| Background and objective:Hypertension is a general chronic disease and the main cause of cardiovascular disease and death.Epidemiological investigation studies found that hypertensive patient often accompanies the metabolic disorder disease such as diabetes,hyperlipidemia.The disorder of glucose and lipid metabolism is also a risk factor for cardiovascular diseases,which not only increases the difficulty of the treatment of hypertension,but also further aggravates the occurrence of cardiovascular events and poor prognosis,seriously threatening human life and health.Therefore,the treatment of hypertension should be comprehensive control of cardiovascular risk,not only to reduce the patient’s blood pressure level,but also to prevent and treat the occurrence of diabetes and hyperlipidemia.At present,the first-line antihypertensive drugs recommended by guidelines are relatively weak in the prevention and treatment of glucolipid metabolism disorders,and some antihypertensive drugs even produce adverse side effects on patients’ glucolipid metabolism.Therefore,the commonly treatment for hypertension complicated with glucolipid metabolism disorder is to use hypoglycemic and lipid-lowering drugs in addition to antihypertensive drugs.Although this treatment regimen is very comprehensive,it will lead to an increase in the types and dosage of drug,thus increasing drug costs and side effects,and reducing patients’ medication compliance.Moreover,this combination therapy is generally not used to prevent abnormal glucose and lipid metabolism in hypertensive patients before they are clinically diagnosed with diabetes or hyperlipidemia.Therefore,it is necessary to explore a drug therapy that can play a role in the co-pathogenesis of hypertension and glucolipid metabolism disorders.Fufang Zhenzhu Tiaozhi Capsule(FTZ,Ingredient: wine privet,bergamot,salt eucommia,bran fried atractylodes macrocephala,panax notoginseng,salvia miltiorrhiza,thistle,coptis chinensis)is an effective prescription obtained by Professor Guo Jiao based on the innovative theory of “Tiaogan Qishu Huazhuo” for the treatment of disorders of glucose and lipid metabolism,including abnormal glucose and lipid metabolism and arteriosclerosis diseases.Previous studies have shown that FTZ can treat diseases such as hyperlipidemia,diabetes,non-alcoholic fatty liver disease,atherosclerosis and osteoporosis by regulating blood lipid and glucose,mitigating insulin resistance,reducing inflammatory factors and oxidative stress injury,etc.However,it is not clear whether FTZ can reduce blood pressure in primary hypertension.Chinese medicine considers that patients with hypertension often show symptoms such as dizziness and headache,which belong to the category of traditional Chinese medicine “vertigo” and“headache”.This closely related to the “gan,pi and shen”.FTZ’s function of“Bushen Tiaogan,Jianpi Huazhuo,Quyu Jiangzhi” conforms to the traditional Chinese medicine syndrome differentiation and treatment of hypertension.Therefore,we speculated that FTZ may have lower blood pressure effect in individual with hypertension.The purpose of the thesis was to investigate whether FTZ to essential hypertension have lower blood pressure and improve glucolipid metabolic disorder of comprehensive prevention and cure function and its mechanism;provide new evidence for the prevention and treatment of hypertension and abnormal glucose and lipid metabolism with traditional Chinese medicine;and provide a new path for the treatment of hypertension.Methods:24 of 8-week-old male spontaneously hypertensive Rat(SHR)were randomly divided into SHR group(n=6),CCB group(n=6),FTZ group(n=6),Combination(CCB+FTZ)group(n=6).The same age Wistar-Kyoto Rat(WKY)were set as control group(n=6).The WKY group and SHR group were given 2.5 m L normal saline,CCB group was given 2.5 m L 10 mg/kg Norvasc(amlodipine besylate),FTZ group was given 2.5 m L 6 g/kg FTZ,CCB + FTZ group was given 1 m L 10 mg/kg Norvasc +1.5 m L 6 g/kg FTZ,qd.The noninvasive caudal blood pressure and weight of rats were measured every two weeks.After 10 weeks of administration,3% pentobarbital sodium(75mg/kg)was injected intraperitoneally to anesthetize the rats,abdominal circumference and body length of rats were measured and Lee’s index was calculated.The blood sample was taken from the abdominal aorta.The left ventricle of rats was harvested and left ventricular mass index(LVMI)was calculated.And epididymis fat(white fat)weight was measured.Hematoxylin-eosin staining(HE),Masson staining,and Sirius Red staining were used to observe the changes of organization morphology,wall to lumen ratio,and CVF.The level of serum matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-inhibitor-1(TIMP-1),Syndecan-1,heparan sulfate(HS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),angiotensin Ⅱ(Ang Ⅱ),Salusin-β,endothelin-1(ET-1),endothelial nitric oxide synthase(eNOs),insulin(INS)and myocardial collagen Ⅰ and Ⅲ were determined by enzyme-linked immunosorbent assay(ELISA).Serum total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),creatinine(CREA),urea nitrogen(BUN)and fasting blood glucose(FBG)were measured by automatic biochemical analyzer.The protein levels of myocardial MMP-9 and aortal syndecan-1 of rats were determined by Western Blots.Results:(1)Compared with WKY group,the blood pressure in SHR group was significantly increased(P<0.05);Compared with SHR group,the blood pressure in CCB group,FTZ group and combination group was significantly decreased(P<0.05);The antihypertensive effect of combination group was significantly better than that of single medication(P<0.05).(2)Compared with WKY group,Lee’s index and white fat weight in SHR group were significantly increased(P<0.05);Compared with SHR group,body weight,Lee’s index and white fat weight in FTZ group and combination group were significantly decreased(P<0.05);The effect of FTZ group and combination group are both more effective than that of CCB group(P<0.05),but there was no statistical difference between FTZ group and combination group(P >0.05).(3)Compared with WKY group,the levels of fasting blood glucose,TC,TG,LDL-C and FIRI were significantly increased in SHR group(P<0.05);Compared with SHR group,serum TC,LDL-C and insulin resistance index in CCB group,FTZ group and combination group were significantly decreased(P<0.05),fasting serum glucose levels in FTZ group and combination group were significantly decreased(P<0.05),and was no significant difference in CCB group(P<0.05);The effect of FTZ group and combination group was better than that of CCB group(P<0.05).(4)Compared with WKY group,LVMI,the cross-sectional area of myocardial cells,the collagen volume fraction and collagen Ⅰ / Ⅲ of myocardial,the wall to lumen ratio and collagen volume fraction of aorta and mesentery in SHR group were significantly increased(P<0.05).Compared with SHR group,LVMI,the cross-sectional area of myocardial cells,the collagen volume fraction and collagen Ⅰ / Ⅲ of myocardial,the wall to lumen ratio and collagen volume fraction of aorta and mesentery were significantly decreased in CCB group,FTZ group and combination group(P<0.05).The effect of combination group was significantly better than that of single medication(P<0.05).(5)Compared with WKY group,the levels of TNF-α,IL-6,AngⅡ,Salusin-β and ET-1 in SHR group were increased,while the levels of eNOs were decreased(P<0.05);Compared with SHR group,the levels of TNF-α,IL-6,AngⅡ,Salusin-β and ET-1 were significantly decreased in CCB group,FTZ group and combination group,while the level of eNOs was significantly increased(P<0.05);The effect of combination group was significantly better than that of single medication(P<0.05).(6)Compared with WKY group,the level of serum syndecan-1 and HS,and the expression of syndecan-1 protein in aorta in SHR group were significantly increased(P<0.05);Compared with SHR group,the level of serum syndecan-1 and HS,and the expression of syndecan-1 protein in aorta were significantly decreased in CCB group,FTZ group and combination group(P<0.05);The effect of combination group was significantly better than that of single medication(P<0.05).(7)Compared with WKY group,the level of serum MMP-9 and MMP-9/TIMP-1,and the expression of MMP-9 protein in myocardial tissue were significantly increased in SHR group(P<0.05);Compared with SHR group,the level of serum MMP-9 and MMP-9/TIMP-1,and the expression of MMP-9 protein in myocardial tissue were significantly decreased in CCB group,FTZ group and combination group(P<0.05);The effect of combination group was significantly better than that of single medication(P<0.05).(8)Compared with WKY group,the level of serum GREA and BUN in SHR group were significantly increased(P<0.05);Compared with SHR group,the level of serum GREA and BUN were significantly decreased in CCB group,FTZ group and combination group(P<0.05);There was no statistical difference between CCB group,FTZ group and combination group(P>0.05).Conclusion:FTZ has a comprehensive effect on the prevention and treatment of hypertension and abnormal glucose and lipid metabolism;and FTZ combined with CCB might improve this effect. |
