水飞蓟素通过调控AMPK/SIRT1途径促进自噬并抑制凋亡减轻大鼠急性肾损伤  

Silymarin Promotes Autophagy and Inhibits Apoptosis by Regulating AMPK/SIRT1 Pathway to Reduce Acute Kidney Injury in Rats

作　　者：李燕菊[1,2] 冯杰 赵婷[1,2] 李红健 马俊鹏[1] 孙力 玛尔江·巴哈提别克[1,2] 王燕 于鲁海[1,2] LI Yanju;FENG Jie;ZHAO Ting(Department of Pharmacy,People’s Hospital of Xinjiang Uygur Autonomous Region,Urumqi,830001)

机构地区：[1]新疆维吾尔自治区人民医院药学部,乌鲁木齐830001 [2]新疆维吾尔自治区临床药学研究所,乌鲁木齐830001

出　　处：《中国中西医结合肾病杂志》2022年第1期11-15,I0002,I0003,共7页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：新疆维吾尔自治区自然科学基金项目(No.2020D01C100)。

摘　　要：目的:探究水飞蓟素对大鼠急性肾损伤(acute kidney injury, AKI)的作用及其可能的作用机制。方法:40只SD大鼠随机分为对照组、模型组、阳性对照组、水飞蓟素组和水飞蓟素+Compound-C组,每组各8只,除对照组外,其余组采用夹闭双侧肾动脉后再灌注法建立AKI模型。HE染色和透射电镜检查肾组织结构变化;Western blot检测肾组织中KIM-1、NGAL、Bax、Bcl-2、LC3、Beclin1、p62、p-AMPKα、AMPKα和SIRT1蛋白表达;全自动生化分析仪检测血清中Scr和BUN水平;TUNEL凋亡检测试剂盒检测细胞凋亡。结果:与对照组相比,模型组大鼠肾组织线粒体结构缺陷,肾损伤评分、细胞凋亡率、KIM-1、NGAL和Bax蛋白表达显著升高(P<0.05),Scr和BUN水平显著升高(P<0.05),Bcl-2、LC3Ⅱ/LC3Ⅰ、Beclin1、p-AMPKα/AMPKα和SIRT1蛋白表达显著降低(P<0.05);与模型组相比,阳性对照组和水飞蓟素组大鼠肾组织病理学变化得到明显改善,肾损伤评分、细胞凋亡率、KIM-1、NGAL、Bax蛋白表达显著降低(P<0.05),Scr和BUN水平显著降低(P<0.05),Bcl-2、LC3Ⅱ/LC3Ⅰ、Beclin1、p-AMPKα/AMPKα和SIRT1蛋白表达显著升高(P<0.05);Compound-C可部分逆转水飞蓟素对AKI大鼠的作用。结论:水飞蓟素可能通过调控AMPK/SIRT1途径促进自噬并抑制凋亡减轻大鼠AKI。Objective:To explore the effect of silymarin on acute kidney injury(AKI) in rats and its possible mechanism. Methods:Forty SD rats were randomly divided into control group, model group, positive control group, silymarin group and silymarin+Compound-C group, each with 8 rats. Except for the control group, AKI models were established by clamping bilateral renal arteries and reperfusion in other groups. HE staining and transmission electron microscopy were used to examine the structural changes of kidney tissue;Western blot was used to detect the expression of KIM-1, NGAL, Bax, Bcl-2, LC3, Beclin1, p62, p-AMPKα, AMPKα and SIRT1 protein in kidney tissue;Automatic biochemical analyzer was used to detect the levels of Scr and BUN in serum;TUNEL apoptosis detection kit was used to detect apoptosis. Results:Compared with the control group, the mitochondrial structure of the kidney tissue of the model group was defective, the renal injury score, apoptosis rate, the expression of KIM-1, NGAL and Bax protein were significantly increased(P<0.05), and the levels of Scr and BUN were significantly increased(P<0.05), the expressions of Bcl-2, LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPKα/AMPKα and SIRT1 protein were significantly reduced(P<0.05);compared with the model group, pathological changes of rat kidney tissue in the positive control group and silymarin group were significantly improved, renal injury score, apoptosis rate, the expressions of KIM-1, NGAL, and Bax protein were significantly reduced(P<0.05), the levels of Scr and BUN were significantly reduced(P<0.05), the expressions of Bcl-2, LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPKα/AMPKα and SIRT1 protein were significantly increased(P<0.05);Compound-C could partially reverse the effect of silymarin on AKI rats. Conclusion:Silymarin may promote autophagy and inhibit apoptosis by regulating AMPK/SIRT1 pathway to reduce AKI in rats.

关 键 词：急性肾损伤 水飞蓟素 自噬 凋亡 AMPK/SIRT1途径 

分 类 号：R285.5[医药卫生—中药学]