The Anti-hypertensive Effect Of The Total Flavonoids Of Averrhoacarambola L.(oxalidacaeae)fruit In Hypertensive Rats Induced By L-NAME And Its Mechanism

Objective: To observe the hypotensive effect of total flavonoids of Averrhoacarambola L.fruit(TFACF)in normal rats and NG-nitro-L-arginine-methyl ester(L-NAME)that induces hypertension in rats and to explore the mechanism of hypotension.Methods: Filter the carambola fruit juice,and add ethanol to reflux.Solution is extracted by petroleum ether,ethyl acetate and N-butanol.After concentrated by rotary evaporators,we use macroporous absorption resin is used to separate the TFACF.Systolic blood pressure(SBP)and diastolic blood pressure(DBP)were recorded by MPA-cardiac function acquisition and analysis system before and after 1?5?10?20?60?90?120?180min,TFACF low dose,TFACF middle dose and TFACF high dose(300mg·kg-1 ? 600mg·kg-1 ? 1200mg·kg-1)was administrated via duodenum of normal rats.Wistar-Kyoto rats were treated intragastrically with L-NAME(50mg·kg-1·d-1)for 4 weeks.50 rats were selected(SBP?140mmHg and/ or DBP?90mmHg)and randomly divided into 5 groups,namely TFACF low dose group(300 mg·kg-1·d-1),middle dose of TFACF group(600 mg·kg-1·d-1),TFACF high dose group(1200 mg·kg-1·d-1),captopril group(10 mg·kg-1·d-1),model control group,and 10 rats in each group.Another 10 normal WKY rats were used as normal group.Systolic blood pressure(SBP)and diastolic blood pressure(DBP)were measured with the tail-cuff method before and after L-NAME induced hypertension in rats treated intragastrically with TFACF(1200,600,300mg·kg-1·d-1)for 5 weeks.After 5 weeks,all rats were anesthetized,with their blood collected and their heart removed.Calculation Left ventricular mass index(LVMI).The content of Ang ?,ET-1,IL-6 and TNF-? in serum were determined by ELISA-kit assay.The content of Nitric oxide(NO)in serum was measured by Nitric oxide synthase(inducible)detection.The content of MDA in serum was determined by thiobarbituric acid.The mrophology changes of the cardiac were observed with HE and Masson staining.The expression of collagen I,collagen III,TNF-?,NF-?B,PPAR-? proteins in cardiac muscle cells were determined by using the immunohistochemical method.The expression of NF-?B in cardiac muscle cells were determined by Real-time PCR.Results: TFACF could remarkably reduce SBP and DBP(P<0.05 or P<0.01)in normal rats,the maximum reduction in blood pressure occurred at20 th minute and could maintain 40 minutes.The more the dose was injected to the rats,the more the blood pressure decrease.The blood pressure would increase gradually after 120 minutes.After intragastric administration of TFACF for 5 weeks,an obvious reduction of blood pressure(P<0.05)occurred in 1th week in high and medium dose of TFACF groups.The blood pressure was maintained at a stable level at fourth weeks in the high dose group.In low dose of TFACF group,an obvious reduction of blood pressure(P<0.05)found in the 2th week.There were not effect on heart rate of TFACF in each dose group and captopril group(P>0.05).Compared with the model group,the LVMI decreased in captopril group and TFACF high dose group(P<0.01).The contents of Ang ?,ET-1,IL-6,MDA and TNF-? in serum of TFACF high dose group decreased(P<0.01),while the contents of NO in serum increased(P<0.01).The contents of MDA and TNF-? in serum of TFACF middle dose and low dose group decreased(P<0.05),while the contents of NO in serum increased,and showed a dose-dependent trend.The cardiomyocyte hypertrophy of TFACF high dose group were relieved.The expression of collagen I,collagen III,TNF-? and NF-?B proteins in cardiac muscle cells were significantly reduced in TFACF high dose group(P<0.01),while the expression of PPAR-? proteins in myocardial cells significantly increased(P<0.01).The expression of NF-?B mRNE in myocardial cells were significantly reduced in TFACF high dose group(P<0.01).Conclusion: TFACF can reduce blood pressure in normal rats and L-NAME will induce hypertension in rats.The mechanism may be related to the regulation of endogenous factors,the relaxation of vascular factor ET-1,Ang II and the contraction of vascular factor NO.Through inhibiting the expression of IL-6 and TNF-?,reducing inflammation,and inhibiting oxidative stress by the PPAR-? and NF-?B pathway.TFACF reduced the deposition of collagen,the degree of myocardial fibrosis in rats and myocardial hypertrophy,so as to protect the rat myocardial cells.