| Chapter One Literature Research Purpose:The paper systematically evaluated the efficacy and safety of Chinese medicine Dilong in the treatment of hypertension.Method : The paper used the computer to retrieve Pub Med,EMbase,The cochrane Library,CBM,the How Net and the Wanfang data,The retrieval time limit was from the establishment of the database to January 1,2018.The two researchers independently screened literature,extracted data,and evaluated the quality of the included randomized controlled trials.They used Revman 5.3 software for meta-analysis.Result: A total of 15 randomized controlled trials were included in the system evaluation,including 1290 patients,677 Chinese medicine groups and 613 control groups.Meta analysis showed that the antihypertensive effect[MD=3.83,95%CI(2.59,5.66),P<0.00001],clinical symptoms[MD=7.09,95%CI(2.36,21.35),P=0.0005],symptom scores[MD=-7.19,95%CI(-11.52,-2.87),P=0.001],mean systolic blood pressure[MD=-6.59,95%CI(-9.40,-3.79),P<0.00001],mean diastolic blood pressure[MD=-2.88,95%CI(-5.66,-0.11),P=0.04],total cholesterol[MD=-0.32,95%CI(-0.52,-0.11),P=0.002],triglyceride[MD=-0.63,95%CI(-1.06,-0.21),P=0.003],blood viscosity[MD=-0.24,95%CI(-0.39,-0.10),P=0.0009]and fibrinogen[MD=-0.42,95%CI(-0.75,-0.09),P=0.01]in the Chinese medicine group were all better than those in the control group,and it was not easy to have adverse reactions[OR=0.15,95%CI(0.04,0.53),P=0.003].The difference between the two groups was statistically significant. Conclusion: The current evidence supports that on the basis of conventional treatment,the Chinese medicine Dilong could significantly reduce blood pressure,relieve clinical symptoms,regulate blood lipids effectively and improve blood circulation.However,due to the limitations of the quality of the research,it should be further confirmed by relevant research.Chapter Two Clinical Research Purpose: 1 To investigate the relationship between hypertensive left ventricular hypertrophy and constitution type of traditional Chinese medicine and further research the correlation between the patient constitution of hypertensive left ventricular hypertrophy and the syndrome type of traditional Chinese medicine.In order to provide evidence for differential diagnosis and differentiation of left ventricular hypertrophy in hypertension,and new ideas and methods for clinical prevention and treatment of left ventricular hypertrophy of hypertension.2 To investigate the efficacy and safety of the Dilong Jiangya Capsule in reducing blood pressure and reversing left ventricular hypertrophy,thus seeking more beneficial treatment for hypertension patients with left ventricular hypertrophy,and providing theoretical basis for the development and application of the Dilong Jiangya Capsule.Method: 1 According to the cross-sectional study of clinical epidemiology,relevant scales and biochemical indicators were developed.2025 patients with hypertension were collected and classified based on the "constitution and classification of traditional Chinese medicine".The paper used Microsoft Excel to establish a database and input data,and SPSS20.0 statistical software to analyze the data.2 Hypertensive patients without left ventricular hypertrophy were randomly divided into the control group and the experimental group.The control group was given the basic treatment of ACEI(Benner Pury)basic therapy plus the intervention of life style.On the basis of the control group,the experimental group was treated with the Dilong Jiangya Capsule.By comparing the condition of blood pressure reducing,the efficiency of blood pressure reducing,the blood pressure changes at different time points,the total symptom scores,the efficiency of clinical symptoms,the changes of biochemical indexes and adverse reactions in the two groups before and after treatment,the effectiveness and safety of the Dilong Jiangya Capsule in the patients with hypertension were evaluated in this paper.3 Hypertensive patients with left ventricular hypertrophy were randomly divided into the control group and the experimental group.The control group was given the basic treatment of ACEI(Benner Pury)basic therapy plus the intervention of life style.On the basis of the control group,the experimental group was treated with the Dilong Jiangya Capsule.By comparing the condition of blood pressure reducing,the efficiency of blood pressure reducing,the blood pressure changes at different time points,the total symptom scores,the efficiency of clinical symptoms,biochemical,plasma PRA,Ag II,ALD and serum SOD,MDA,GSH in the two groups before and after treatment,the effectiveness and safety of the Dilong Jiangya Capsule in the patients with hypertensive left ventricular hypertrophy were evaluated in this paper.Result: 1 In 2025 patients with hypertension,the distribution of physical characteristics was Qi deficiency(20.28%)>Yin deficiency(15.72%)>Yang deficiency(14.1%)>Phlegm dampness(13.89%)>Blood stasis(10.54%);the proportions of five types of physique of qi deficiency,yin deficiency,Yang deficiency,phlegm dampness and blood stasis were also an absolute high value,the distribution sequence of other biased constitutions was Qi Yu quality(6.54%)>Damp-heat(4.32%)>special constitution(0.12%);The characteristics of the distribution of TCM syndrome type were liver-fire excess type(36.8%)>type of deficiency of Yin leading to hyper activity of Yang(30.1 %)>stagnation of phlegm-dampness type(29.1%)>kidney deficiency type(3.9%).The distribution characteristics of TCM syndrome type of hypertensive left ventricular hypertrophy were Phlegm Stasis Syndromes(47.12%)>Yin deficiency and Yang hyperactivity(20.18%)>deficiency of both Yin and Yang(17.44%)>overabundant liver-fire syndrome(15.26%).2 By comparing blood pressure changes of hypertensive patients without left ventricular hypertrophy at different time points during the treatment,there was no significant difference in systolic blood pressure between the control group and the experimental group in the first,second week(P>0.05),the amplitude of systolic blood pressure in the experimental group was better than that of the control group in the fourth,eighth weeks,had significant difference(P<0.05);and the diastolic blood pressure between the control group and the experimental group in the first week had no difference(P>0.05),the diastolic blood pressure in the experimental group was better than that of the control group in the second,fourth,eighth weeks,had significant difference(P<0.05),and buck trend was more obvious over time.the total score of the symptoms post-treatment in the control group and the experimental group was lower than prior treatment,and according to research result,the total score of the symptoms in the experimental group post-treatment was reduced more obviously than the total score of the control group.And the efficiency of clinical symptoms in the experimental group was statistically different(P<0.01).There was no significant difference in blood lipid,blood sugar and renal function in the control group between prior treatment and post-treatment,and had significant difference(P>0.05);there was no significant change in blood sugar,high density lipoprotein and renal function in the experimental group between prior treatment and post-treatment,however,the total cholesterol, glycerol three,and low density lipoprotein were lower in the experimental group than post-treatment,they were all statistically different(P<0.05).3 During the treatment of hypertensive patients with left ventricular hypertrophy,there was no obvious discrepancy in the control group and the experimental group in the first week(P>0.05),the amplitude of systolic blood pressure in the experimental group was better than that of the control group in the second,fourth,eighth weeks,and there was no obvious discrepancy in the control group and the experimental group in the first week(P>0.05),the diastolic blood pressure in the experimental group was better than that of the control group in the second,fourth,eighth weeks,had significant difference(P<0.05),and buck trend was more obvious over time.the total score of the symptoms post-treatment in the control group and the experimental group was lower than prior treatment,and had significant difference.the total score of the symptoms in the experimental group post-treatment was reduced more obviously than the total score of the control group,and had significant difference(P <0.05).Compared with the control group,the efficiency of clinical symptoms in the experimental group was statistically different(P<0.05).There was no significant difference in blood lipid,blood sugar and renal function in the control group between prior treatment and post-treatment,had no significant difference;there was no significant change in blood sugar in the experiment group between prior treatment and post-treatment,however,the total cholesterol,triglycerides,high-density lipoprotein were increased in the experiment group than post-treatment,they were all statistically different(P<0.05).Compared with the control group of prior treatment,the level of renin activity in the control group was significantly lower than that in post treatment,had significant difference;the plasma angiotensin II and aldosterone levels in the control group of post treatment were significantly lower,the difference was statistically significant(P <0.01).The plasma renin activity and aldosterone levels of the experimental group of post treatment were significantly lower,the difference was statistically significant(P <0.01).Compared with the control group of post treatment,the plasma renin activity and plasma angiotensin II in the experimental group of post treatment were significantly lower,had significant difference,aldosterone levels had decreased.Compared with the control group of prior treatment,the level of serum SOD in the control group of post treatment was higher,had significant difference(P <0.05);the level of serum MDA in the control group of post treatment was higher,had significant difference.Compared with the experiment group of prior treatment,the level of serum SOD was higher but the level of serum MDA was significantly lower than that in the experiment group of post treatment,had significant difference.Compared with post treatment,the level of serum SOD was higher but the level of serum MDA was significantly lower than that in the experiment group of post treatment,had significant difference.Conclusion: 1 The result of the investigation showed that five kinds of hypertension patients were Qi deficiency,Yang deficiency,Yin deficiency,phlegm and blood stasis,blood stasis and the Phlegm Stasis Syndromes were higher in patients with hypertensive left ventricular hypertrophy than other syndromes.Combining the onset of hypertensive left ventricular hypertrophy with the prognosis,the constitution of the patients,and the symptoms of this stage,we would better practice the concept of "regulating body" and "treating no disease" in traditional Chinese Medicine.2 Dilong Jiangya Capsule with removing phlegm and stasis and activating blood and dredging collaterals had the effect on reducing the blood pressure and symptom score of hypertensive left ventricular hypertrophy in patients with phlegm and blood stasis syndrome,improving the effective rate of clinical symptoms,reversing myocardial remodeling,and could reduce RAS system and oxidative stress factor level.Chapter Three Experimental Research Purpose: Based on Rho/ROCK signal pathway,the effect mechanism of Dilong Jiangya Capsule on spontaneous hypertension,rat blood pressure and resistance to left ventricular hypertrophy was studied.Method: A model of hypertensive left ventricular hypertrophy was established in the paper,the research objects were divided into the model group,the step-down group,the Benner Pury group and the other WKY group,body weight,blood pressure and heart rate were monitored in each group.Plasma renin activity,angiotensin II,aldosterone,SOD,malondialdehyde and glutathione content were measured by Elisa.Through observation of rat heart color Doppler ultrasound,HE staining,Masson staining,cardiac index,electron microscope,the paper evaluated the morphology and function of SHR-induced left ventricular hypertrophy in rats.The RAS system and the oxidative stress factor network with mediated of Rho/ROCK signaling pathway were detected by the protein-gene level.Result: 1 General situation There was no death during the whole experiment,the rats in the WKY group were full of energy,sensitive activity and shiny body hair,they were no obvious attack when grabbed;in the model group,the rats were poor in spirit,less active,less shiny,irritability and irritability,and there were obvious aggressive when grabbed;The rats in the Dilong Jiangya group and the Benner Pury group were in the spirit of recovery after 2 weeks of continuous administration,and the activity was good,the body hair and attack behavior when grabbed were obviously better than the model group.2 Weight There was no significant difference in weight of the experimental groups at the beginning of the experiment(P > 0.05),during the experiment,the weight of rats in WKY group was heavier than that of model group at part times,but at the end of the experiment,there was no significant difference in weight of the rats in each group(P >0.05).3 Systolic blood pressure,Diastolic blood pressure Systolic blood pressure: the rats were administered for 2 weeks,6 weeks,10 weeks,Systolic blood pressure of the Dilong Jiangya group and the Benner Pury group were lower than the model group,the difference was statistically significant(P<0.05,P<0.01);the rats were administered for 2 weeks,Systolic blood pressure of the Benner Pury group was superior to that of the Dilong Jiangya group,the difference was statistically significant(P<0.05).But the rats were administered for 6 weeks,10 weeks,compared with Systolic blood pressure between the Dilong Jiangya group and the Benner Pury group,the difference was not statistically significant(P> 0.05).Diastolic blood pressure: the rats were administered for 2 weeks,6 weeks,10 weeks,Diastolic blood pressure of the Dilong Jiangya group and the Benner Pury group were lower than the model group,the difference was statistically significant(P<0.05,P<0.01);the rats were administered for 2 weeks,6 weeks,10 weeks,compared with Diastolic blood pressure between the Dilong Jiangya group and the Benner Pury group,the difference was not statistically significant(P> 0.05).4 Heart rate Administered for 2 weeks: The heart rate of WKY group and Benner Pury group was lower than that of the model group,the difference was statistically significant(P<0.05,P<0.01);compared with the model group,the heart rate of the depressor group was reduced,the difference was not statistically significant(P> 0.05).Administered for 6 weeks and 10 weeks: The heart rate of WKY group,the Dilong Jiangya group and Benner Pury group was lower than model group,the difference was statistically significant(P<0.05,P<0.01);the heart rate of Benner Pury group was compared with that of the Dilong Jiangya group,the difference was statistically significant(P<0.05).5 Renin,Angiotensin II and Aldosterone The model group,the Dilong Jiangya group and the Benner Pury group were all higher than those in the WKY group,the difference was statistically significant(P<0.01,P<0.05);The Dilong Jiangya group and the Benner Pury group were all lower than the model group,the difference was statistically significant(P<0.05).6 SOD?MDA and GSH The comparison of serum SOD and GSH : The model group,the Dilong Jiangya group and the Benner Pury group were all lower than those in the WKY group,the difference was statistically significant(P<0.05);The Dilong Jiangya group and the Benner Pury group were all higher than the model group,the difference was statistically significant(P<0.05).The comparison of serum MDA : The model group,the Dilong Jiangya group and the Benner Pury group were all higher than those in the WKY group,the difference was statistically significant(P<0.01,P<0.05);The Dilong Jiangya group and the Benner Pury group were all lower than the model group,the difference was statistically significant(P<0.05).7 UCG Compared with the WKY group,the LVDd,LVDs,IVSd,LVIVSs,LVPWd,LVPWs and FS of the model group,the Dilong Jiangya group and the Benner Pury group were significantly increased,the LVEF of the model group,the Dilong Jiangya group and the Benner Pury group were all significantly decreased,and the difference was statistically significant(P<0.05).Compared with the model group,the LVDd,LVDs,IVSd,LVIVSs,LVPWd,LVPWs and FS of the Dilong Jiangya group and the Benner Pury group were significantly decreased,and the difference was statistically significant(P<0.05).The LVEF of the Dilong Jiangya group and the Benner Pury group were all significantly increased,and the difference was statistically significant(P<0.05).8 Cardiac index Compared with the WKY group,the Cardiac weight of the model group,the Dilong Jiangya group and the Benner Pury group were increased.Compared with the model group,the Cardiac weight of the Dilong Jiangya group and the Benner Pury group were significantly decreased(P<0.05).Comparison of Cardiac weight between the Dilong Jiangya group and the Benner Pury group,the difference was not statistically significant(P>0.05).Compared with the WKY group,the Cardiac index of the model group,the Dilong Jiangya group and the Benner Pury group were significantly increased(P<0.05).The Cardiac index of the Dilong Jiangya group and the Benner Pury group were significantly decreased.Between the Dilong Jiangya group and the Benner Pury group,the difference was not statistically significant(P>0.05).9 HE staining Under the light microscope,the myocardial cells of WKY group were clear and orderly arranged,and no myocardial fibers were destroyed.The nuclei were clear and the cell gap was not changed.Compared with the WKY group,the myocardial cells in the model group were significantly increased and disordered,the nuclei were enlarged,the interstitial spaces were widened,a large number of collagen fibers proliferated in the tissues,and infiltration of inflammatory cells around the tissues.Compared with the model group,the myocardial fibrillation in the Dilong Jiangya group and the Benner Pury group was more orderly and infiltration of inflammatory cells was decreased.10 Masson staining Myocardial bundles of the WKY group had less collagen fibers,mainly distributed around blood vessels.In the model group had a large number of collagen fibers hyperplasia,myocardial muscle bundle gap increased to varying degree,and myocardial cell interstitial and paravascular fibers were significantly increased and disorganized,accompanied by severe collagen deposition.Compared with the model group,the fibrosis of cardiomyocytes in the Dilong Jiangya group and the Benner Pury group were significantly reduced,and the myocardial muscle bundles were arranged neatly,but the focal focal collagen fibers were still visible.Compared with the WKY group,the myocardial histopathological area of the model group,the Dilong Jiangya group and the Benner Pury group were increased.Compared with the model group,the myocardial histopathological area of the Dilong Jiangya group and the Benner Pury group were significantly decreased(P <0.05).11 Electron microscope The myofibrils of the WKY group were arranged periodically,the Z line was clear,the mitochondria were arranged regularly,the mitochondrial crista was clear and tidy.In the model group,myofibrils were broken,most of the Z lines were broken and/or disappeared,the number of mitochondria increased,most mitochondria were swollen,mitochondria cristae were arranged in disorder,interstitial fibrosis was observed in many fields.The myofibrils of the Dilong Jiangya group and the Benner Pury group were broken,the Z line was discontinuous,the mitochondria were slightly swelling and swollen,and the mitochondrial crista was arranged in disorder.12 Immunohistochemistry AT1:The brown yellow granules in the WKY group were expressed weakly positive,and the brown yellow granules in the model group were strongly positive,and the brown yellow granules in the Dilong Jiangya group and the Benner Pury group showed moderate positive expression.CTGF:The brown yellow granules in the WKY group were expressed weakly positive,and the brown yellow granules in the model group were strongly positive.The brown granules increased significantly and showed a moderate positive expression in the Dilong Jiangya group,while the brown granules in the Benner Pury group increased slightly and showed a moderate positive expression.13 q RT-PCR method detection i NOS:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).e NOS:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05).ACE1:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05); Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).ACE2:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05).AT1:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).CTGF:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).Rho A:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).ROCK:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.01,P<0.05,P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).?-SMA:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.01,P<0.05,P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05).Col III:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all up-regulated,the difference was statistically significant(P<0.01,P<0.05,P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all down-regulated,the difference was statistically significant(P<0.05). 14 Western-blot method detection i NOS:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).e NOS:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05).ACE1:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);The Benner Pury group was lower than model group,the difference was statistically significant(P<0.05).ACE2:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.01?P<0.05?P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05).AT1:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).CTGF:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).Rho A:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).MYPT1:Compared with the model group,the difference between the Dilong Jiangya group and the Benner Pury group was not statistically significant(P> 0.05).p-MYPT1:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).Col III:Compared with the WKY group,the model group,the Dilong Jiangya group and the Benner Pury group were all increased,the difference was statistically significant(P<0.05);Compared with the model group,the Dilong Jiangya group and the Benner Pury group were all decreased,the difference was statistically significant(P<0.05).Conclusion: The blood pressure of rats with spontaneously hypertensive could be reduced by the Dilong Jiangya Capsule.It could reverse the left ventricular hypertrophy of hypertension to a certain extent with the treatment of removing phlegm and removing blood stasis and activating blood circulation and collaterals.Hypertensive left ventricular hypertrophy may be related to Rho / ROCK signaling pathway by the RAAS system and oxidative stress factors induced. |
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