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目的:观察福辛普利(fosinopril)和氯沙坦(losartan)对自发性高血压大鼠(SHR)肾脏Klotho表达及氧化应激的影响,探讨其对高血压肾损伤的保护作用机制。方法:15只22周龄雄性SHR,随机分为3组(5只/组);模型组(SHR组),福辛普利组[10mg/(kg.d)],氯沙坦组[50mg/(kg.d)];以22周龄雄性Wistar-Kyoto(WKY)大鼠5只为正常对照,共喂养8周。检测尾动脉收缩压、24h尿蛋白定量(Upro)、尿N-乙酰-8-D-氨基葡萄糖苷酶(NAG酶)等指标。HE染色观察大鼠肾脏病理改变,RT-PCR、免疫组织化学及Western印迹检测Klotho蛋白及mRNA表达;并检测肾脏总抗氧化能力(T-AOC)、丙二醛(MDA)、铜锌超氧化物歧化酶(Cu/Zn-SOD)、锰超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)水平。结果:模型组肾脏出现高血压肾损伤的病理特征。与模型组比较,福辛普利或氯沙坦组收缩压、Upro及尿NAG酶均明显降低,肾脏病理损伤减轻(P<0.05)。肾脏Klotho蛋白及mRNA表达均明显上调(P<0.05),同时肾脏MDA含量降低,T-AOC,Cu/Zn-SOD,CAT及GSH-Px活性均较模型组增加(P<0.05或P<0.01),Mn-SOD活性无明显改变(P>0.05)。结论:福辛普利、氯沙坦可通过上调抗衰老基因Klotho在肾脏中的表达,并抑制氧化应激,从而对高血压肾损伤起保护作用。
AIM: To observe the effect of fosinopril and losartan on Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and to explore the protective mechanism of fosinopril and losartan on hypertensive renal injury. Methods: Fifteen 22-week-old male SHRs were randomly divided into 3 groups (5 rats / group), model group (SHR group) and fosinopril group (10 mg / (kg · d) / (kg.d)]. Five male Wistar-Kyoto (WKY) rats at 22 weeks of age were fed for 8 weeks. Tail artery systolic pressure, 24h urine protein (Upro), urinary N-acetyl-8-D-glucosaminidase (NAG enzyme) and other indicators. The pathological changes of rat kidney were observed by HE staining. The expressions of Klotho protein and mRNA were detected by RT-PCR, immunohistochemistry and Western blotting. T-AOC, MDA, Cu / Zn-SOD, Mn-SOD, CAT and GSH-Px were measured. Results: The kidney of model group showed hypertensive kidney injury pathological features. Compared with model group, the systolic blood pressure, Upro and urinary NAG enzyme in fosinopril or losartan group were significantly lower than those in model group, and renal pathological damage was alleviated (P <0.05). The protein and mRNA expressions of Klotho in kidney were significantly up-regulated (P <0.05), meanwhile, the content of MDA in kidney decreased and the activities of T-AOC, Cu / Zn-SOD, CAT and GSH-Px increased ), Mn-SOD activity did not change significantly (P> 0.05). Conclusion: Fosinopril and losartan can protect renal hypertensive rats by up-regulating the expression of anti-aging gene Klotho in kidney and inhibiting oxidative stress.