| Objective: To study the renal protection effect of Tribulus terrestris(TT) in obesity-related hypertensive rats, through the application of modern molecular biology techniques such as PCR, immunohistochemistryand protein electrophoresis. To explore the preliminary pharmacological mechanism of TT,by obseve the regulation of TT on the aciviation of RAAS and retention of water and sodium in kidney.Methods:1. The establishment of obesity-related hypertensive rats and characteristic of renal injury: 70 wistar rats were fed with high-fat diet while 10 wistar rats were fed with regular diet for 25 weeks. 32 from 70 rats were selected into model group with the standard that both the body weights and blood pressure were 25% more than those of the average in control group after 25 weeks. 8 from 32 rats were included into experiment 1. Body weightsand blood pressure were measured regularly. The concentration of triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C) in serum was measured by biochemical methods, and the level of leptin(Lep), angiotensinⅡ(AngⅡ), β2-microglobulin(β2-MG) in serum were determined by ELISA. Morphological changes of aorta, adipose tissue and kidney were observed by HE staining. The distribution of TGF-β1in kidney was observed by immunohistochemical staining.2. The pharmacodynamical study of Tribulus terrestrisin the treatment of obesity-related hypertension: 24 obesity-related hypertensive rats were randomly divided into 3 groups with 8 rats per group: TEL group(3.4g?kg-1?d-1Telmisartan), TT group(17.2 g?kg-1?d-1 TT), model group(the same solume of saline). Rats were given drugs or saline by intragastric administration for 12 weeks. Body weight and blood pressure were measured every week. The concentration of serum TG, TC, HDL-C and LDL-C were measured by biochemical methods and morphological changes of aorta and adipose tissue by HE staining.3. The pharmacological study of Tribulus terrestrisin the treatment of obesity-related hypertension by regulating renal function:After the experiment 2, the concentration of AngⅡ, Lep, AVP and β2-MG were assayed using ELISA kits. The distribution of AT1 receptor、Lep R and TGF-β1 on kidney were observed by immunohistochemical staining. Thedistribution of Lep R 、 AT1 and TGF-β1in kidney was observed by immunohistochemical staining.Levels of m RNA expression of PKA, AT1, JAK2, STAT3、AT2 and AQP2 in kidney were determined by quantitive real-time PCR(q RT-PCR). Levels of protein expression of PKA, JAK2 and STAT3 in kidney were determined by western blotting.Results:1. Experiment 1: Body weights and blood pressure of model group rats were increased significantly(P<0.05). The level of serum TC, LDL-C, Lep,β2-MG and AngⅡof model group rats increased significantly(P<0.05). Endothelia injury and smooth muscle cell proliferation were found in aorta of model group, TGF-β1 in kiney of group model increased significantly(P<0.05)..2. Experiment 2:Body weights and blood pressure of TT group decreased(P<0.05). The level of serum TG、TC and LDL-C of TT group decreased significantly(P<0.05) Aortic morphology of TT group was improved obviously and the size of lipocyte decreased.3. Experiment 3: The level of AngⅡ, Lep, AVP and β2-MG in serum of TT group decreased significantly(P<0.05). The density of AT1R、Lep R and TGF-β1 in kidney of TT group decreased significantly(P<0.05). The m RNA expression of JAK2, STAT3, PKA, AQP2 and AT1 R in kidney of TT group decreased significantly(P<0.05).The protein expression of PKA、JAK2 and STAT3 in kidney of TT group decreased significantly(P<0.05).Conclusion:(1)Tribulus terrestris can lose weight and reduce the blood pressure and blood fat content of obesity-related hypertensive rats.(2) Tribulus terrestris can inhibit the JAK2/STAT3 mediated by leptin in obesity-related hypertensive rats.(3) Tribulus terrestris can inhibit the pathway of RAAS and AVP\PKA\AQP2 against water sodium retention in the obesity-related hypertensive rats. |
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