發(fā)布時間：2018-08-13 13:44

【摘要】：目的：明確普伐他汀(Pravastatin)對大鼠腎缺血再灌注(ischemia-repe rfusion,I/R)損傷的保護作用,并探討其作用的分子機制。 方法：健康Sprague-Dawley大鼠被分為假手術組(Sham,n=5)；缺血再灌注組(I/R,n=8)和普伐他汀預處理組(P+I/R,n=8).I/R組和P+I/R組大鼠給予雙側腎動脈夾閉45min后恢復灌注,術后24h后處死大鼠。P+I/R組大鼠術前1周給予普伐他汀(20mg/kg/d)灌胃。檢測各組大鼠腎功能、體質量和血脂變化。過碘酸雪夫(PAS)染色觀察腎組織病理改變；免疫組化法檢測腎組織熱休克蛋白70(HSP-70)蛋白表達；TUNEL法和免疫印跡法檢測細胞凋亡相關蛋白Bcl-2、Bax和活性天冬氨酸特異性胱氨酸蛋白酶-3(活性Caspase-3)的變化。 結果：與對照組相比,普伐他汀預處理組大鼠腎組織HSP-70蛋白表達明顯增加[(173.9±19.2)%比(100.9±13.7)%,P0.01]。與Sham組相比,I/R組大鼠Scr、血BUN水平升高；腎組織壞死評分增高[(36.0±1.2)%比0,P0.01]、TUNEL陽性細胞數(shù)增多[(295.4±28.3)%比(1.4±1.1)%,P0.01]。與Sham組相比,I/R組大鼠腎組筆Bcl2/Bax蛋白表達下降[(57.3±7.3)%比(100.0±5.4)%,P0.01],活性Caspase-3蛋白表達增高[(385.2±38.7)%比(96.9±3.1)%,P0.01]。P+工/R組大鼠上述指標的改變減輕(P0.05) 結論：普伐他汀預處理可保護大鼠腎I/R損傷,其腎臟保護作用機制與誘導介質HSP-70蛋白有關,而不依賴其降脂作用。
[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 鹵19.2)% vs (100.9 鹵13.70)%, P0.01]. Compared with the Sham group, the serum BUN level and the renal necrosis score increased [(36.0 鹵1.2)% vs 0 (P0.01)] in the I / R group [(295.4 鹵28.3)% vs (1.4 鹵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 鹵7.3)% vs (100.0 鹵5.40)%], and the expression of active Caspase-3 protein increased [(385.2 鹵38.7)% vs (96.9 鹵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.
【學位授予單位】：延邊大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R692

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