| 摘要: |
| 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. |
| 关键词: 肾切除术 肾功能不全 葡萄糖代谢障碍 肾素-血管紧张素系统 AMP活化蛋白激酶 |
| DOI：10.3724/SP.J.1008.2015.00761 |
| 投稿时间：2014-09-19修订日期：2015-01-17 |
| 基金项目:国家自然科学基金(81270934). |
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| Renin-angiotensin system blockade in correction of glucose metabolic disturbance in uninephrectomized rats |
| YANG Ke-ke,MOU Xue-jing,SHEN Jian,ZHAO Hai-lu |
(Guangxi Key Laboratory of Diabetic System Medicine, Guilin Medical University, Guilin 541004, Guangxi, China
*Corresponding author) |
| Abstract: |
| Objective To investigate influences of renin-angiotensin system (RAS) blocker on glucose metabolism and expression of AMP-activated protein kinase (AMPK) in renal cortex in uninephrectomized (UNX) rats. Methods A total of 40 rats were divided into four groups, namely, sham, uninephrectomy, UNX rats treated with angiotensin converting enzyme inhibitor (ACEI) Lisinopril and angiotensin receptors blockade (ARB, n=10) Losartan. Rats in the last three groups were made into UNX model reserving single right kidney. Fasting blood samples were collected for measurements of glucose metabolism-related parameters in UNX rats at 3, 6, 8, and 10 months after operation, and renal function-related parameters at 10 months; the expression of AMPK in renal cortex tissues was detected by Western blotting analysis and immunofluorescence in the four groups. Results Compared with the sham rats, UNX rats developed hyperinsulinemia at 3 months after operation, hyperglycemia at 8 months and increased homeostasis model assessment-insulin resistance (HOMA-IR) at 3 and 10 months (P <0.05 for the corresponding parameters). Compared with UNX rats, ACEI and ARB treatments significantly improved hyperinsulinemia, hyperglycemia and HOMA-IR (P <0.05). Compared with the sham rats, UNX rats developed renal dysfunction as reflected by significantly high serum urea (P <0.05), creatinine (P <0.05) and ratio of urinary total protein to creatinine (P <0.05) at 10 months after operation; while these parameters were all significantly decreased in ACEI or ARB rats (P <0.05) compared with UNX rats. Meanwhile, AMPK expression in the renal cortex tissues in UNX rats was the least among the four groups (P <0.01), and those in the ACEI and ARB groups were significantly higher than that in the UNX group (P <0.01). Conclusion RAS blockade may correct glucose metabolic disorders caused by uninephrectomy via restoring AMPK expression, which may serve as a potential therapeutic target for renal dysfunction accompanied with glucose dysmetabolism. |
| Key words: nephrectomy renal insufficiency glucose metabolism disorders renin-angiotensin system AMP-activated protein kinase |
