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目的探讨肾素-血管紧张素系统(renin-antiotensin system,RAS)阻滞剂对单肾切除大鼠糖代谢和肾皮质腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)表达的影响。方法大鼠随机均分为假手术组(Sham)、单肾切除组(uninephrectomy,UNX)、血管紧张素转化酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)治疗组(ACEI组)和血管紧张素受体阻滞剂(angiotensin receptor blocker,ARB)治疗组(ARB组,n=10),后3组切除左肾制备单侧肾切除大鼠模型。术后3、6、8、10个月测定大鼠糖代谢相关指标;术后10个月测定大鼠肾功能相关指标,蛋白免疫印迹法和免疫荧光法检测大鼠右肾皮质中AMPK的表达。结果与Sham组相比,UNX组大鼠术后3个月出现空腹血胰岛素升高(P<0.05),8个月出现空腹血糖升高(P<0.05),3、10个月出现HOMA-IR升高(P<0.05);与UNX组相比,ACEI和ARB治疗组空腹血胰岛素、空腹血糖、HOMA-IR值均降低(P<0.05)。与Sham组相比,UNX组大鼠术后10个月出现血尿素氮、血肌酐和尿总蛋白/肌酐比值升高(P<0.05);与UNX组相比,ACEI和ARB治疗组血尿素氮、血肌酐和尿总蛋白/肌酐比值均降低(P<0.05)。与Sham组相比,UNX组大鼠残留肾中AMPK表达减少(P<0.01);与UNX组相比,ACEI和ARB治疗组残留肾中AMPK表达升高(P<0.01)。结论 RAS阻滞剂可通过恢复肾皮质AMPK的表达来纠正单肾切除引起的糖代谢异常,是临床肾功能不全伴糖代谢异常潜在的治疗靶标。
Objective To investigate the effects of renin-antiotensin system (RAS) blockade on glucose metabolism and AMP-activated protein kinase (AMPK) expression in single-nephrectomized rats. Methods The rats were randomly divided into sham group, uninephrectomy group (ACXX), angiotensin converting enzyme inhibitor (ACEI) group and angiotensin The rats in ARB group (n = 10) were treated with angiotensin receptor blocker (ARB). The indexes of glucose metabolism in rats were measured at 3, 6, 8 and 10 months after operation. The indices of renal function in rats were measured at 10 months after operation. The expression of AMPK in rat right renal cortex was detected by Western blotting and immunofluorescence staining . Results Compared with Sham group, fasting blood insulin level increased (P <0.05) and fasting blood glucose level increased (P <0.05) in UNX group 3 months after operation, and HOMA- IR increased (P <0.05). Compared with the UNX group, the fasting blood insulin, fasting blood glucose and HOMA-IR of ACEI and ARB treatment groups were decreased (P <0.05). Compared with Sham group, the blood urea nitrogen, serum creatinine and total urinary protein / creatinine ratio increased significantly in UNX group 10 months after operation (P <0.05). Compared with UNX group, Nitrogen, serum creatinine and urinary total protein / creatinine ratio were decreased (P <0.05). Compared with Sham group, the expression of AMPK in residual kidney of rats in UNX group decreased (P <0.01). Compared with UNX group, the expression of AMPK in residual kidney of ACEI group and ARB group increased (P <0.01). Conclusion RAS blockers can correct the abnormal glucose metabolism caused by single nephrectomy by restoring the expression of AMPK in renal cortex, which is a potential therapeutic target of clinical renal dysfunction with abnormal glucose metabolism.