依那普利对自发性高血压大鼠肾组织AngⅡ和TGF-β/Smads变化及肾纤维化的影响

Effects of enalapril on the levels of AngⅡand TGF-β/Smads and renal fibrosis in spontaneously hypertensive rats

目的探讨依那普利对自发性高血压大鼠(SHR)肾组织血管紧张素Ⅱ(AngⅡ)和TGF-β/Smads通路相关因子m RNA表达的影响。方法20只雄性SHR随机分成模型组和依那普利组;另取雄性Wistar-Kyoto(WKY)大鼠10只作为对照组。依那普利组给药剂量为1.05 mg/(kg·d),每日1次灌胃,持续10周,模型组和对照组灌胃等量生理盐水。每2周监测1次血压,10周后处死动物并取材。使用脲酶法检测各组大鼠血尿素氮(BUN)水平,采用酶联免疫吸附测定(ELISA)i法检测各组AngⅡ、血清胱抑素C(CysC)、尿微量白蛋白(m ALB)水平,Masson染色观察大鼠肾组织病理变化,实时荧光定量PCR检测肾组织中AngⅡ、转化生长因子β1(TGF-β1)、Smad2、Smad3、Ⅰ型胶原(CollagenⅠ)和Ⅳ型胶原(CollagenⅣ)的m RNA相对表达量。结果给药前(0周),与对照组相比,模型组和依那普利组大鼠收缩压与舒张压均显著升高(P<0.05);与模型组比较,依那普利组收缩压与舒张压差异无统计学意义(P>0.05);药物干预后,与模型组比较,依那普利组的收缩压与舒张压均显著下降(P<0.05)。与对照组比较,模型组AngⅡ、BUN、CysC和尿m ALB水平明显升高(P<0.05);肾组织出现大量蓝色胶原纤维沉积,同时AngⅡ、TGF-β1、Smad2、Smad3、CollagenⅠ和CollagenⅣ的m RNA相对表达量明显升高(P<0.05)。与模型组相比,依那普利组肾组织胶原纤维沉积程度明显减轻,血清及肾组织中上述指标均明显下降(P<0.05)。结论依那普利可对SHR起到稳定的降压作用,并通过降低AngⅡ的水平、抑制TGF-β/Smads信号通路的表达,减轻肾纤维化,改善高血压导致的肾损伤。

ObjectiveTo investigate the effect of enalapril on angiotensin(Ang)Ⅱand TGF-β/Smads in renal tissue of spontaneously hypertensive rats(SHR).MethodsA total of 20 male SHRs were randomly divided into model group and enalapril group.Ten male Wistar Kyoto rats(WKY)were taken as control group.The dosage of enalapril was 1.05 mg/(kg·d),once a day,for 10 weeks.The model group and the control group were given the same amount of normal saline.Blood pressure was monitored every two weeks regularly.After 10 weeks animals were killed and tissue samples were collected.Urease method was used to detect the blood urea nitrogen(BUN)content.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of AngⅡ,serum cystatin C(CysC)and urinary microalbumin(mALB).Masson staining was used to observe the renal pathological changes.Real-time PCR was used to detect the relative mRNA expressions of AngⅡ,transforming growth factorβ1(TGF-β1),Smad2,Smad3,CollagenⅠand CollagenⅣ.ResultsCompared with the control group,the systolic and diastolic blood pressures increased significantly in the model group and enalapril group(P<0.05).There were no significant differences in the systolic and diastolic blood pressures between the model group and enalapril group(P>0.05).After drug intervention,compared with the model group,the systolic and diastolic blood pressures decreased significantly in enalapril group(P<0.05).Compared with the control group,the levels of AngⅡ,BUN,CysC and urinary mALB were significantly increased in the model group(P<0.05).A large number of blue collagen fibers were deposited in renal tissue,and the relative mRNA expressions of AngⅡ,TGF-β1,Smad2,Smad3,CollagenⅠand CollagenⅣwere significantly increased(P<0.05).Compared with the model group,the level of collagen deposition was significantly reduced in renal tissue,and the above indexes in serum and kidney decreased significantly in enalapril group(P<0.05).ConclusionEnalapril has a stable hypertensive effect on SHR,and it can alleviate renal fibrosis and improve renal injury caused by hypertension by lowering AngⅡlevel and inhibiting the expression of TGF-β/Smads signaling pathway.