| ObjectivesOur population is aging,and as hypertension affects most elderly people,these individuals are more likely to have organ damage or clinical cadiovasular diseases.Which leads to serious economic and medical burden for our society.The proportion of hypertensive patiets with isolated systolic hypertension(ISH)increases with age-60%of patiets with ISH>60 years of age.These diseases that coronary heart disease,heart failure,cerebrovascular disease,kidney failure,diabetes mellitus are highly prevalent.So the goal of hypertension in the elderly is not only blood pressure control,but also protecting organ damage and improving quality of life.Our research group thought that deficiency of the kidney is basic pathogenesis,and phlegm-heat and blood stasis is the pathological factors.According to our research,phlegm-heat accounts for(59%)and blood stasis(39%).Therefore,we put forward that Reinforcing Kidney and Activating Blood Circulation and resolving phlegm Formula may improve quality of life.Related research found that theraphy of strengthening kidney and activating circulation,therapy of replenishing kidney-essence and removing phlegm can achieve efficacy in hypertension and cardiac remodeling,and reverse caediac fibrosis by inhibiting TGF β 1 signalling,our pre-experiment found that Reinforcing Kidney and Activating Blood Circulation and resolving phlegm Formula could decrease the wet weight of left ventricle of Spontaneously hypertensive rats,and suppressed the expression of Smad3.As a consequence,we put forward that Reinforcing Kidney and Activating Blood Circulation and resolving phlegm Formula may improve quality of life of hypertension in the elderly.and reverse cardiac remodeling of Spontaneously hypertensive rats by suppressing TGFβ1 signalling.1.Reinforcing Kidney and Activating Blood Circulation and resolving phlegm Formula play a role in quality of life of elderly hypertensive patients by way of Randomized Controlled Blind Trial.2.Exploring the acute toxicity in Reinforcing Kidney and Activating Blood Circulation and resolving phlegm Formula.3.Pathological mechanism of Spontaneously Hypertensive Rat is similar to human’s,and SHR is the best animal model for hypertension.We discussed the Therapeutic effect of Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula in blood pressure,cross-sectional area of left ventricular,fibrosis area of left ventricular,wet weight of left ventricular,the thickness of interventricular septum and the left ventricular posterior wall.4.Because of diversity and complexity of TGFβ1(Transforming growth factorl)signaling pathway,We discussed the mechanism of Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula in smad-related signaling and non-smad-related signaling which be involed in left ventricular remodeling.MethodsThe part of clinical study:A total of 80 elderly patients with hypertension were enrolled and randomly assigned to receive Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula plus standard medications for the treatment of hypertension or just standard medications.The endpoint was the blood pressure,clinical symptoms,SF-36 scores during 2 weeks of treatment.The part of experimental study:1.32 NIH mice were randomly assigned to be given Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula or distilled water for two weeks,and we observed the behavior everyday,weight,and anatomy at day 14.2.50 spontaneously hypertensive rats were randomly assigned to four groups:low dose group,middle dose group,high dose group,and blank control group,wky as normal control for 8 weeks,we took Blood pressure of SHR and wky every week.3.Cross-sectional area(CSA)of left ventricular,fibrosis area of left ventricular,wet weight of left ventricular,the thickness of interventricular septum,the left ventricular posterior wall,myofibril were evaluated by echocardiography,histology,immunofluorescence,electron microscope.4.TGFβ1、Smads、TAK1、AT1R were examined by western blot,RT-PCR to verify the mechanism of Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula on left ventricular remodeling of SHR.ResultsThe part of clinical study:1.The changes in blood presssre of elderly hypertensive patients with Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm FormulaThe study showed statistically significant clinical impact of systolic blood pressure(P<0.05),but it is not in diastolic blood pressure(P>0.05).2.The change in SF-36 scores of elderly hypertensive patients with Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm FormulaResults Contrast experimental group and control group,there was a significant deviation(P<0.05),therapeutic effect of experimental group surpass control group.3.The changes in symptom scores of pain and dizzness in elderly hypertensive patients with Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula.The effect on symptom scores of pain and dizzness in experimental group was more obvious than that in control group(P<0.05).The part of experimental study:1.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula has no bad effct on behavior,weight and gross anatomy,which means no acute toxicity in mice(P>0.05).2.The changes in blood pressure,morphology of left ventricular muscle and protein expression between SHR group and WKY group.The study suggested statistically significant clinical impact of systolic blood pressure(P<0.05),so it is diastolic blood pressure(P<0.05),Blood pressure of SHR is higher than that of WKY;there is statistical significance in cross-sectional area of left ventricular(P<0.05),fibrosis area of left ventricular(P<0.05),wet weight of left ventricular(P<0.05),the thickness of interventricular septum(P<0.05),the left ventricular posterior wall(P<0.05)between SHR group and WKY group.The protein expression is significantly higher than WKY group in TGFβ1(P<0.05),Smad3(P<0.05),TAK1(P<0.05),The protein expression of TAK1 increased with SHR age(10W WKY,10W SHR,14W SHR,17W SHR)(P<0.05).3.The changes in blood pressure between SHR groups and WKY group with Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula lowered systolic blood pressure in low-dose group,middle-dose group and high-dose group(P<0.05),and the systolic blood pressure of high-dose group declined more than that low-dose group,middle-dose group(P<0.05).In diastolic blood pressure of rats,middle-dose group and high-dose group showed curative effect(P<0.05),but not in low-dose group(P>0.05).4.The changes in morphology of rats with Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula.there was statistical significance in cross-sectional area of left ventricular(P<0.05),fibrosis area of left ventricular(P<0.05),wet weight of left ventricular(P<0.05),between SHRL and SHRW.But there were no the changes in low-dose group,middle-dose group and high-dose group(P>0.05);Myocardial myofibril was be developed in SHRL,and Myocardial myofibril arranged in disorder in SHRW.5.The mechanism of Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula on TGFβ1 signaling.Expression of Smads and TAK1 were suppressed in SHRL(P<0.05).Conclusions1.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula decrease systolic blood pressure,improve symptoms,and develop quality of life in hypertension with elderly.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula is a new therapy for treating elderly patiets with hypertension.2.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula decline blood pressure and reverse the cardiac remodeling of SHR.3.Reinforcing Kidney and Activating Blood Circulation and Resolving Phlegm Formula maybe improve cardiac remodeling by TGFβ1 signaling. |
