普伐他汀对大鼠肾缺血再灌注损伤的保护作用及机制探讨

发布时间：2018-08-13 13:44

【摘要】：目的：明确普伐他汀(Pravastatin)对大鼠肾缺血再灌注(ischemia-repe rfusion,I/R)损伤的保护作用,并探讨其作用的分子机制。方法：健康Sprague-Dawley大鼠被分为假手术组(Sham,n=5)；缺血再灌注组(I/R,n=8)和普伐他汀预处理组(P+I/R,n=8).I/R组和P+I/R组大鼠给予双侧肾动脉夹闭45min后恢复灌注,术后24h后处死大鼠。P+I/R组大鼠术前1周给予普伐他汀(20mg/kg/d)灌胃。检测各组大鼠肾功能、体质量和血脂变化。过碘酸雪夫(PAS)染色观察肾组织病理改变；免疫组化法检测肾组织热休克蛋白70(HSP-70)蛋白表达；TUNEL法和免疫印迹法检测细胞凋亡相关蛋白Bcl-2、Bax和活性天冬氨酸特异性胱氨酸蛋白酶-3(活性Caspase-3)的变化。结果：与对照组相比,普伐他汀预处理组大鼠肾组织HSP-70蛋白表达明显增加[(173.9±19.2)%比(100.9±13.7)%,P0.01]。与Sham组相比,I/R组大鼠Scr、血BUN水平升高；肾组织坏死评分增高[(36.0±1.2)%比0,P0.01]、TUNEL阳性细胞数增多[(295.4±28.3)%比(1.4±1.1)%,P0.01]。与Sham组相比,I/R组大鼠肾组笔Bcl2/Bax蛋白表达下降[(57.3±7.3)%比(100.0±5.4)%,P0.01],活性Caspase-3蛋白表达增高[(385.2±38.7)%比(96.9±3.1)%,P0.01]。P+工/R组大鼠上述指标的改变减轻(P0.05) 结论：普伐他汀预处理可保护大鼠肾I/R损伤,其肾脏保护作用机制与诱导介质HSP-70蛋白有关,而不依赖其降脂作用。
[Abstract]:Aim: to investigate the protective effect of pravastatin (Pravastatin) on renal ischemia reperfusion injury in rats and to explore its molecular mechanism. Methods: healthy Sprague-Dawley rats were divided into sham-operated group (Shamma group), ischemia reperfusion group (I / R group) and pravastatin preconditioning group (P / R rnm8). The I / R group and Pi / R group were given bilateral renal artery occlusion (45min) to restore perfusion. The rats in the Pi / R group were given pravastatin (20mg/kg/d) 1 week before operation. Renal function, body mass and blood lipid were measured. The expression of heat shock protein 70 (HSP-70) in renal tissue was detected by immunohistochemistry. The changes of apoptosis-related protein Bcl-2 Bax and active aspartate specific cystine-3 (Caspase-3) were detected by TUNEL and Western blotting. Results: compared with the control group, the expression of HSP-70 protein was significantly increased in pravastatin preconditioning group [(173.9 卤19.2)% vs (100.9 卤13.70)%, P0.01]. Compared with the Sham group, the serum BUN level and the renal necrosis score increased [(36.0 卤1.2)% vs 0 (P0.01)] in the I / R group [(295.4 卤28.3)% vs (1.4 卤1.11) P 0.01]. Compared with the Sham group, the expression of Bcl2/Bax protein in the renal tissue of rats in the I / R group decreased [(57.3 卤7.3)% vs (100.0 卤5.40)%], and the expression of active Caspase-3 protein increased [(385.2 卤38.7)% vs (96.9 卤3.1) P0.01] .The changes of the above indexes in the P / R group were alleviated (P0.05) conclusion: pravastatin pretreatment can protect the renal IR injury of rats. The mechanism of renal protection is related to the induction of HSP-70 protein, but not dependent on its lipid-lowering effect.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692

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