八厘麻毒素的降压与肾脏保护作用

Rhomotoxine's antihypertensive effect and its protection on kidney

目的探讨八厘麻毒素长期灌胃给药的降压和肾脏保护作用以及该作用与血管紧张素Ⅱ(AngⅡ)及内皮型一氧化氮合成酶(eNOS)之间的关系。方法 35只14周龄自发性高血压大鼠(SHR),随机分为5组(n=7):八厘麻毒素大剂量组、八厘麻毒素中剂量、八厘麻毒素小剂量组、卡托普利组和SHR模型组。7只W istar大鼠作为空白对照组。灌胃给药6周后,测量各组大鼠尾动脉压和心率;检测血浆和肾脏AngⅡ含量和eNOS含量;观察肾脏病理改变,图像分析软件分析肾小管损伤指数。结果与空白对照组比较,SHR模型组血压显著升高(P<0.01),心率增快(P<0.01);AngⅡ含量明显升高(P<0.01),而eNOS含量明显降低(P<0.01)。八厘麻毒素各剂量均能明显降低血压和减慢心率(P<0.01),并不同程度降低AngⅡ含量(P<0.05或P<0.01),升高eNOS含量(P<0.05或P<0.01)。HE染色见空白对照组大鼠肾脏结构基本正常,SHR模型组大鼠肾小球萎缩、硬化,肾小动脉管壁增厚,肾小管间质损伤系数较空白对照组明显升高(P<0.01),各药物治疗组均不同程度改善肾脏的病理变化,减轻肾小管间质损伤(P<0.01)。结论八厘麻毒素对SHR具有良好的降压、减慢心率与肾脏保护作用,其机制可能与降低AngⅡ含量,升高eNOS含量以及减慢心率有关。

Objective To explore rhomotoxine＇s antihypertensive effect and its protection on kidney,and their relationships with levels of Ang II and eNOS in plasma and local kidney in spontaneously hypertensive rats（SHR）.Methods Thirty-five SHR rats aged 16 weeks were randomly grouped（n=7 each）： high dose rhomotoxine group,middle dose rhomotoxine group,low dose rhomotoxine group,captopril group and SHR model group.Seven Wistar rats were served as the control group.After drugs were given intragastrically for 6 weeks,blood pressure and heart rate were monitored by tail-cuff method.The contents of AngⅡand eNOS in the plasma and kidney were detected by radioimmunoassay and ELISA respectively.Results Compared with control rats,the rats in SHR model group exhibited increased blood pressure and heart rate（P0.01）,higher AngⅡand lower eNOS levels in the plasma and kidney（P0.01）;atrophy and sclerosis in glomeruli and greater coefficient of renal interstitial injury（P0.01）.In groups with rhomotoxine treatments,blood pressure obviously lowered while heart rate decreased as compared to the SHR model group,and rhomotoxine lowered AngⅡ while increased eNOS,and decreased pathological injures in kidney.Conclusion Rhomotoxine decreases blood pressure and heart rate markedly,and it has protective effect on kidney in SHR rats.The mechanisms may relate to a decrease in Ang II,an increase in eNOS and a decrease in heart rate.