【摘要】：目的：明確普伐他汀(Pravastatin)對(duì)大鼠腎缺血再灌注(ischemia-repe rfusion,I/R)損傷的保護(hù)作用,并探討其作用的分子機(jī)制。 方法：健康Sprague-Dawley大鼠被分為假手術(shù)組(Sham,n=5)；缺血再灌注組(I/R,n=8)和普伐他汀預(yù)處理組(P+I/R,n=8).I/R組和P+I/R組大鼠給予雙側(cè)腎動(dòng)脈夾閉45min后恢復(fù)灌注,術(shù)后24h后處死大鼠。P+I/R組大鼠術(shù)前1周給予普伐他汀(20mg/kg/d)灌胃。檢測(cè)各組大鼠腎功能、體質(zhì)量和血脂變化。過(guò)碘酸雪夫(PAS)染色觀察腎組織病理改變；免疫組化法檢測(cè)腎組織熱休克蛋白70(HSP-70)蛋白表達(dá)；TUNEL法和免疫印跡法檢測(cè)細(xì)胞凋亡相關(guān)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(jié)果：與對(duì)照組相比,普伐他汀預(yù)處理組大鼠腎組織HSP-70蛋白表達(dá)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(píng)分增高[(36.0±1.2)%比0,P0.01]、TUNEL陽(yáng)性細(xì)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(dá)下降[(57.3±7.3)%比(100.0±5.4)%,P0.01],活性Caspase-3蛋白表達(dá)增高[(385.2±38.7)%比(96.9±3.1)%,P0.01]。P+工/R組大鼠上述指標(biāo)的改變減輕(P0.05) 結(jié)論：普伐他汀預(yù)處理可保護(hù)大鼠腎I/R損傷,其腎臟保護(hù)作用機(jī)制與誘導(dǎo)介質(zhì)HSP-70蛋白有關(guān),而不依賴(lài)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(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R692

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