红景天苷调节AMPK/mTOR/ULK1信号通路对结肠癌SW480细胞裸鼠的肝脏损伤的影响  

Influence of Salidroside on Liver Injury in Nude Mice with Colon Cancer SW480 Cells by Regulating AMPK/mTOR/ULK1 Signaling Pathway

作　　者：王浩 刘志毅 张斌 曹宽 王人颢 WANG Hao;LIU Zhi-yi;ZHANG Bin;CAO Kuan;WANG Ren-hao(Graduate School of Xuzhou Medical University,Xuzhou,Jiangsu,221004,China;Hepatobiliary Pancreatic Surgery,Xuzhou Medical University Affiliated Hospital,Xuzhou,Jiangsu,221004,China)

机构地区：[1]徐州医科大学研究生院,江苏徐州221004 [2]徐州医科大学附属医院肝胆胰外科,江苏徐州221004

出　　处：《现代生物医学进展》2023年第17期3226-3231,共6页Progress in Modern Biomedicine

基　　金：江苏省自然科学基金面上项目(BK20191153)。

摘　　要：目的:探讨红景天苷(Sal)调节单磷酸腺苷活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/Unc51样激酶1(ULK1)信号通路对结肠癌SW480细胞裸鼠肝脏损伤的影响。方法:通过皮下注射SW480细胞悬浮液建立肝转移裸鼠模型,将造模后的裸鼠随机分为模型组、Sal低剂量(Sal-L,50 mg/kg Sal)组、Sal中剂量(Sal-M,100 mg/kg Sal)组、Sal高剂量(Sal-H,200 mg/kg Sal)组,Sal-H+AMPK抑制剂(Compound C,200 mg/kg Sal+10 mg/kg Compound C)组,以未接种SW480细胞悬液的裸鼠作为对照组。腹部主动脉取血,检测裸鼠血清中丙氨酸氨基转移酶(AST)、天冬氨酸氨基转移酶(ALT)水平;处死裸鼠,检测肝转移瘤数目及肝脏重量;HE染色观察肝脏组织病理变化;qRT-PCR检测肝脏组织中AMPK、mTOR、ULK1 mRNA表达水平;Western blot检测肝脏组织中自噬(Beclin1、p62)蛋白及通路相关蛋白表达。结果:与对照组相比,模型组裸鼠组织中出现肝转移瘤,肝脏重量、AST、ALT水平、mTORmRNA、ULK1mRNA、p62表达显著增加(P<0.05);Beclin1、AMPKmRNA及蛋白表达显著降低(P<0.05);与模型组相比,Sal-L、Sal-M、Sal-H组肝转移瘤数目、肝脏重量、AST、ALT水平、mTORmRNA、ULK1 mRNA、p62表达显著降低(P<0.05);Beclin1、AMPK mRNA及蛋白表达显著增加(P<0.05);与Sal-H组相比,Sal-H+Compound C组肝转移瘤数目、肝脏重量、AST、ALT水平、mTORmRNA、ULK1mRNA、p62表达显著增加(P<0.05);Beclin1、AMPKmRNA及蛋白表达显著降低(P<0.05)。结论:Sal可通过减少裸鼠肝转移瘤形成,保护裸鼠肝脏,其机制可能与激活AMPK/mTOR/ULK1信号通路,促进肝脏自噬有关。Objective:To investigate the influence of salidroside(Sal)on liver injury in nude mice with colon cancer SW480 cells by regulating adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/Unc51-like kinase 1(ULK1)signaling pathway.Methods:Liver metastasis nude mice model was established by subcutaneous injection of SW480 cell suspension,and the nude mice after modeling were randomly grouped into model group,low-dose Sal(Sal-L,50 mg/kg Sal)group,medium-dose Sal(Sal-M,100 mg/kg Sal)group,high-dose Sal(Sal-H,200 mg/kg Sal)group,Sal-H+AMPK inhibitor(Compound C,200 mg/kg Sal+10 mg/kg Compound C)group,and nude mice not inoculated with SW480 cell suspension were performed as the control group.Blood was collected from the abdominal aorta,the serum levels of alanine aminotransferase(AST)and aspartate aminotransferase(ALT)in nude mice were observed.The nude mice were sacrificed,and the number of liver metastases and liver quality were detected.HE staining was used to observe the pathological changes of liver tissue.The expression levels of AMPK,mTOR and ULK1 mRNA in liver tissue were detected by qRT-PCR.Western blot was used to detect the expression of autophagy(Beclin1,p62)proteins and pathway-related proteins in liver tissue.Results:Compared with the control group,liver metastases appeared in the nude mice of the model group,the liver weight,levels of AST and ALT,the mTORmRNA,ULK1 mRNA,and the expression of p62 were obviously increased(P<0.05).The mRNA and protein expressions of Beclin1 and AMPK were obviously decreased(P<0.05).Compared with the model group,the number of liver metastases,liver weight,levels of AST and ALT,the mTORmRNA,ULK1 mRNA,and the expression of p62 in the Sal-L,Sal-M,and Sal-H groups were obviously decreased(P<0.05).The mRNA and protein expressions of Beclin1 and AMPK were obviously increased(P<0.05).Compared with the Sal-H group,the number of liver metastases,liver weight,levels of AST and ALT,the mTORmRNA,ULK1 mRNA,and the expression of p62 in the Sal-H+Compound C

关 键 词：红景天苷 AMPK/mTOR/ULK1信号通路 SW480细胞 裸鼠 肝脏 

分 类 号：R-33[医药卫生] R735.7