丹参酮ⅡA对大鼠缺血再灌注肾组织AMPK/ULK1通路的影响  

Effect of tanshinone ⅡA on AMPK/ULK1 pathway in rat renal tissue of ischemia-reperfusion

作　　者：顾晖[1] 汤霆 李勇[1] 廖莎[1] 皮倩[1] 张柏银[1] 唐吉伟[1] GU Hui;TANG Ting;LI Yong;LIAO Sha;PI Qian;ZHANG Boyin;TANG Jiwei(Brain Hospital of Hunan Province,Changsha 410007,Hunan,China)

机构地区：[1]湖南省脑科医院

出　　处：《现代中西医结合杂志》2020年第2期120-123,162,共5页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：湖南省卫计委科研计划课题(B20180102;B20180714)

摘　　要：目的观察丹参酮ⅡA对大鼠肾缺血再灌注后腺苷单磷酸激活蛋白激酶(AMPK)/自噬激活激酶1(ULK1)通路的影响,探讨其肾脏保护的作用机制。方法将30只健康雄性Wistar大鼠随机分为丹参酮ⅡA组、缺血再灌注组、假手术组,每组10只。丹参酮ⅡA组于缺血前30 min尾静脉注射丹参酮ⅡA注射液0.5 mg/kg,假手术组和缺血再灌注组注射等量的生理盐水。丹参酮ⅡA组和缺血再灌注组通过双侧肾蒂夹闭45 min的方法建立肾缺血再灌注模型,假手术组打开腹腔后不夹闭双侧肾蒂。再灌注24 h后心脏采血,检测血清肌酐(Cr)、尿素氮(BUN)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平;取肾组织,采用HE染色观察各组肾组织病理改变,Western blot法测定肾组织中AMPK、ULK1表达水平。结果缺血再灌注组大鼠血清Cr、BUN、TNF-α、IL-6、IL-10水平及肾组织中AMPK、ULK1表达水平均明显高于假手术组(P均<O.05);丹参酮ⅡA组大鼠血清Cr、BUN、TNF-α、IL-6水平及肾组织中AMPK、ULK1表达水平均明显低于缺血再灌注组(P均<0.05),血清IL-10水平明显高于缺血再灌注组(P<0.05);丹参酮ⅡA组大鼠肾组织病理学改变明显轻于缺血再灌注组。结论丹参酮ⅡA能减轻肾缺血再灌注造成的肾损伤,其可能通过抑制AMPK/ULK1通路调控自噬,减轻肾脏炎症反应而起肾脏保护作用。Objective It is to observe the effect of tanshinoneⅡA on the expression of adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)pathway and to explore the mechanism of its renal protection Methods 30 healthy Wistar male rats were randomly divided into 3 groups:tanshinoneⅡA group,ischemia-reperfusion group(IR group)and the sham operation group,each group had 10 rats.The tanshinoneⅡA group was injected with tanshinone IIA injection 0.5 mg/kg from tail vein at 30 minutes before ischemia,the sham operation group and IR group were injected with an equal amount of normal saline.The bilateral renal pedicles was clamped for 45 points to establish the models of renal ischemia-reperfusion in the tanshinoneⅡA group and the IR group,the bilateral renal pedicles were not clamped after opening the abdominal cavity in the sham operation group.At 24 hours of perfusion,cardiac blood was collected to determine the levels of serum creatinine(Cr)and urea nitrogen(BUN),tumor necrosis factor-ɑ(TNF-ɑ),interleukin-6(IL-6)and IL-10 by ELISA.Renal tissues were taken and the pathological changes of renal tissues were observed by HE staining.Western blot was used to determine the expression levels of AMPK and ULK1 in renal tissues.Results The levels of serum Cr,BUN,TNF-ɑ,IL-6 and IL-10 and the expression levels of AMPK,ULK1 in renal tissue in the IR group were significantly higher than those in the sham operation group(P<0.05).The levels of serum Cr,BUN,TNF-ɑ,IL-6 and the expression levels of AMPK,ULK1 in renal tissue in the tanshinoneⅡA group were significantly lower while the level of serum IL-10 was higher than those in the IR group(P<0.05).The pathological changes of renal tissue in tanshinoneⅡA group were significantly lighter than that in IR group.Conclusion TanshinoneⅡA can alleviate the damage caused by renal ischemia-reperfusion,which may inhibit autophagy and reduce renal tissue inflammation by inhibiting AMPK/ULK1 pathway to achieve the role of protection for kidn

关 键 词：缺血再灌注损伤 丹参酮ⅡA 肾损伤 AMPK/ULK1通路 自噬 

分 类 号：R-332[医药卫生]