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苯那普利对糖尿病大鼠肾皮质p21CIP1蛋白表达的调节及其机制 |
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林善锬 吴永贵 余毅 周江华
【摘要】 目的 研究苯那普利对糖尿病大鼠肾皮质p21CIP1 蛋白表达的调节及其 机制。方法大鼠随机分单侧肾切除对照组、糖尿病组及糖尿病苯那普利(10mg.kg-1.日-1，灌胃)治疗组。应用Northern杂交检测各组肾皮质转化生长因子β1(TGFβ1)mRNA表达，Western杂交检测各组肾皮质TGFβ1及p21CIP1蛋白的表达。另外，血浆、肾皮、髓质血管紧张素转换酶(ACE)活性由荧光分光光度法测定。结果 糖尿病大鼠一周后体重即明显下降(P＜0.05)，伴肾重/体重明显增加(P＜0.05)，血浆ACE活性有所下降而肾皮质ACE活性则有所上升。Northern杂交表明糖尿病组肾皮质TGFβ1 mRNA表达约比对照组上升63.6%。肾皮质TGFβ1及P21CIP1蛋白表达也明显增加；苯那普利治疗一周对肾脏肥大有明显的抑制作用，对血浆、肾皮、髓质ACE活性抑制分别达89.0%、70.0%、70.5%，对肾皮质TGFβ1 mRNA及TGFβ1和p21CIP1蛋白表达抑制分别达47.7%，49.5%，60.0%。结论 苯那普利可抑制糖尿病肾脏早期p21CIP1蛋白高表达，其机制可能部分与高调TGFβ1表达有关。
【关键词】 苯那普利 糖尿病肾病 p21CIP1蛋白 转化生长因子β1
Regulation of renal cortex p21CIP1protein expression by benazepril and its mechanism in diabetic rats
LIN Shanyan,WU Yonggui,YU Yi,et al.
Division of Nephrology,Hua Shan Hospital,Shanghai Medical University,Shanghai,200040
【Abstract】 Objective To investigate the regulation of renal cortex p21CIP1 protein expression by benazapril and its mechanism in diabetic rats. Methods The rats were randomly divided into following groups: uninephrectomized rats, streptozotocin-induced diabetic rats and diabetic rats treated with benazepril (10mg.kg-1.d-1, by gavage). Angiotensin converting enzyme (ACE) activities were determined by fluorimetric assay in plasma and renal cortex and medulla. Renal cortex transforming growth factor β1 (TGFβ1) mRNA expression was assessed by Northern blot analysis, and TGFβ1 and p21CIP1protein expression was measured by Western blot analysis. Results After 1 week, diabetic rats developed a body weight loss, an increased kidney weight/body weight and an elevated ACE activity in renal cortex despite a decreased ACE activity in plasma. Northern blot analysis showed that renal cortex TGFβ1 mRNA expression in diabetic rats increased by 63.6%, as against uninephrectomized rats. Western blot analysis noted that TGFβ1 and p21CIP1 protein expres[1] [2] 下一页
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