瞬时感受器电位离子通道香草素受体亚家族4激动剂对缺血再灌注肾损伤的保护作用及机制

Protective effects of transient receptor potential vanilloid 4 agonist on ischemia-reperfusion-induced acute kidney injury of rats and mechanism

目的 观察瞬时感受器电位离子通道香草素受体亚家族4（TRPV4）激动剂对缺血再灌注肾损伤的保护作用,并探讨其作用机制.方法 建立大鼠肾缺血再灌注模型,将实验动物随机分为3组：假手术组、缺血再灌注组、治疗组（各8只）.治疗组大鼠给TRPV4激动剂GSA1016790A（30 μg/kg）,缺血再灌注组给予相同量的生理盐水,假手术组不夹闭肾蒂,余处理同缺血再灌注组.各组分别检测血清肌酐、尿素氮水平,组织病理检查,同时行免疫组织化学、Western blot及实时定量聚合酶链反应（Real-time PCR）检测肾组织中TRPV4及内皮型一氧化氮合酶（eNOS）的表达.结果 GSK1016790A可以改善缺血再灌注急性肾损伤的组织损伤.与缺血再灌注组比较,治疗组中血清肌酐及尿素氮水平显著降低[（228.4±32.62） μmol/L比（123.62±21.23） μmol/L、（35.65±13.9） μmol/L比（20.93±9.6）μmol/L,P＜0.05],免疫组织化学及Real-time PCR检测显示TRPV4及eNOS的表达明显升高（P＜0.05）.结论 TRPV4激动剂GSA1016790A可通过血管舒张改善缺血再灌注急性肾损伤.

Objective To study the protective effect of transient receptor potential vanilloid 4 （TRPV4） on ischemia-reperfusion （I/R） kidney injury in rats and the action mechanism.Methods I/R acute kidney injury （AKI） model was established in SD rats.Rats were randomly assigned to the following groups：（1） sham ＋ saline group （n=8）;（2） I/R ＋ saline group （n=8）;（3） I/R ＋ GSK1016790A group （n =8）.The rats were intraperitoneally injected either with solvent （sham group and I/R group）,and GSK1016790A （30 μg/kg body weight） in I/R ＋ GSK1016790A group before the start of ischemia.Respectively.The levels of blood urea nitrogen and creatinine were measured.The expression of TRPV4 and endothelial nitric oxide synthase （eNOS） was detected by immunohistochemistry,and real-time quantitative polymerase chain reaction （Real-time PCR）,respectively.Results GSK1016790A ameliorated the histologic damage of rats with I/R-induced AKI.Compared to I/R ＋ saline group,the levels of serum creatinine and urea nitrogen were significantly reduced in I/R ＋ GSK1016790A group [（228.4 ± 32.62） μmol/L vs.（123.62 ±21.23） μmol/L,and （35.65 ± 13.9） μmol/L vs.（20.93 ±9.6） μmol/L,respectively,P ＜0.05].The TRPV4 and eNOS expression was increased after GSK1016790A treatment （P ＜ 0.05）.Conclusion Activation of TRPV4 can ameliorate I/R-induced AKI by the way of eNOS-mediated vasodilation.