摘要
目的探讨葛根素(puerarin,Pue)对D-氨基半乳糖所致小鼠急性肝衰竭(ALF)的保护作用及初步观察其作用机制。方法将50只昆明小鼠随机分为5组,造模前两周Pue组、LY294002组(LY组)、Pue+LY组尾部静脉注射300mg/kgPue、10mg/kgLY和300mg/kgPue+10mg/kgLY,每天1次,正常对照组和模型组给予等量无菌生理盐水,末次给药后禁食24h,除正常组外,其他组腹腔注射半乳糖构建ALF模型,正常对照组注射等量无菌生理盐水。生化反应仪检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸基转移酶(AST)、总胆红素(TBil)水平,试剂盒法检测肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)含量;HE染色、TUNEL染色和蛋白免疫印迹法分别检测小鼠肝脏组织的病理学变化、肝细胞凋亡数量和P-Akt、P-GSK-3β、cleaved caspase-3蛋白表达水平。结果与正常对照组相比,模型组小鼠肝细胞凋亡数量,血清ALT、AST、Tbil水平,肝组织MDA含量及cleavedcaspase-3蛋白表达水平明显升高(P<0.05),SOD、GSH-Px含量及P-Akt、P-GSK-3β蛋白表达水平明显下降(P<0.05);Pue组治疗后,与模型组相比,Pue组中各指标的变化均明显改善(P<0.05),LY组、Pue+LY组与模型组相比组间差异无统计学意义(P>0.05)。结论Pue可能通过激活PI3K/Akt信号通路,从而减轻肝功能的损伤程度,发挥对D-氨基半乳糖诱导的ALF小鼠肝脏的保护作用。
Objective To investigate the protective effect of puerarin(Pue)on acute liver failure(ALF)induced by d-galactosamine in mice and its mechanism.Methods Fifty Kunming mice were randomly divided into five groups.Two weeks before modeling,the Pue group,LY294002 group(LY group),and Pue+LY group were injected with 300 mg/kg Pue,10 mg/kg LY,or 300 mg/kg Pue+10 mg/kg LY,respectively,into the caudal vein once daily.The normal control and model group rats were administered the same amount of sterile physiological saline.After the final administration and fasting for 24 h,the ALF model was established by intraperitoneal injection of galactose in all groups except the control group which received the same amount of sterile normal saline.Serum levels of alanine aminotransferase(ALT),aspartate transferase(AST),and total bilirubin(TBil)were detected by a biochemical analyzer,and levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in liver tissues were detected by kits.Hematoxylin and eosin staining,TUNEL staining,and western blotting were used to detect pathological changes in the mouse liver tissue,apoptosis in liver cells,and the expression levels of P-Akt,P-glycogen synthase kinase(GSK)-3β,and cleaved caspase-3 protein,respectively.Results Compared with the control group,significant increases were detected in the number of apoptotic hepatocytes,serum ALT,AST,and TBil levels,the liver tissue MDA content,and cleaved caspase-3 protein expression levels in the model group(P<0.05),while protein expression levels of SOD,GSH-Px,P-Akt,and P-GSK-3βwere significantly decreased(P<0.05).After treatment,all indices in the Pue group were significantly improved compared with the model group(P<0.05),while there were no significant differences between indices among the LY group,Pue+LY group,and model group(P>0.05).Conclusions Puerarin may play a protective role in the liver of mice with d-galactosaminoglycan-induced acute liver failure by activating the PI3K/Akt signaling pathway,thereby reducing the degree of liver function damage.
作者
刘英辉
周东方
金国华
闫文昭
程欣
LIU Yinghui;ZHOU Dongfang;JIN Guohua;YAN Wenzhao;CHENG Xin(The Third Hospital of Hebei Medical University,Shijiazhuang 050000,China)
出处
《中国比较医学杂志》
CAS
北大核心
2019年第8期68-74,共7页
Chinese Journal of Comparative Medicine
基金
河北省卫生和计划生育委员会基金项目(G201734)
