去肾交感神经术对自发性高血压大鼠肾胺酶及酪氨酸羟化酶的影响

摘要

目的:通过观察自发性高血压大鼠(SHR)去肾交感神经手术前后血压、肾胺酶浓度、肾脏酪氨酸羟化酶(TH)与肾胺酶表达水平的变化,探讨去肾交感神经术降低血压的可能机制.方法:将SHR大鼠(n=48)随机分为基线组、手术组、假手术组和对照组,同批同周龄WKY大鼠(n=12)作为基线对照组,同条件喂养至12周龄测各组血压,首批处死SHR基线组、WKY组,采血、取肾脏组织送检；手术组、假手术组与对照组继续监测血压,于去肾交感神经术后1,6周时分批处死每组大鼠各6只,分别采血、取肾脏组织送检.采用ELISA方法测定血浆肾胺酶浓度,Western印迹测定肾脏TH、肾胺酶蛋白表达水平.结果:与WKY组大鼠比较,SHR基线组大鼠血压、肾脏TH蛋白表达水平明显升高(p＜0.05),血浆肾胺酶浓度及蛋白表达水平明显下降(P＜0.05)；术后1周,手术组大鼠平均动脉压与TH蛋白表达水平较基线组明显降低且明显低于假手术组及对照组(P＜0.05),手术组肾胺酶水平较基线组明显增高并明显高于假手术组及对照组(P＜0.05)；术后6周,手术组平均动脉压与TH水平较术后1周上升而肾胺酶浓度及水平较术后1周降低,较基线组、假手术组与对照组差异无统计学意义(P＞0.05)；假手术组与对照组较基线组各项指标差异无统计学意义(P＞0.05).结论:去肾交感神经术降低血压的作用可能与其抑制交感神经,升高肾胺酶浓度及其蛋白表达水平有关.%Objective: To investigate the impact of renal denervation on the blood pressure, plasma renalase content and expression of renalase and tyrosine hydroxylase (TH) in the idney of spontaneous hypertensive (SH) rats and to explore the role of renal denervation in lowering the blood pressure. Methods: SH rats were randomly assigned into a baseline group, a surgery (renal denervation) group, a sham group and a control group (n=48). WKY rats matched in age (n=12) served as a baseline control group. All rats were housed until 12 weeks old. Then, the rats in the baseline group and the WKY group were sacrificed whose blood and kidney were collected for examination. In the renal denervation group, the sham group and the control group, the blood pressure was monitored continuously. One week and 6 weeks after the renal denervation, 6 rats in each group were sacrificed whose blood and kidney were collected. ELISA was employed to measure the plasma renalase and Western blot assay done to detect the expression of TH and renalase in the kidney. Results: Compared with WKY rats, blood pressure significantly increased and TH protein expression markedly elevated (P<0.05) in SH rats in the baseline group, but plasma renalase content and protein expression of renalase in the kidney dramatically reduced (P<0.05). One week after the surgery, the mean arterial pressure and TH protein expression in the surgery group were lowered compared with the baseline group and dramatically reduced compared with the sham group and the control group (P<0.05). In the surgery group, the renalase level was markedly increased compared with the baseline group, the sham group, and the control group (P<0.05). Six weeks after the renal denervation, the mean arterial pressure and TH level in the surgery group were significantly increased but the renalase content and expression markedly reduced compared with those 1 week, but there were no marked differences among the surgery group, the sham group, and the control group (P>0.05). No pronounced differences in the above variables were found between the sham group and the control group at any time point (P>0.05).rnConclusion: Renal denervation can lower the blood pressure, which may attribute to the suppression of sympathetic nerves, increase in plasma renalase content and renalase expression in the kidney.