葛根素基于肝脏Dusp9-ASK1信号通路对非酒精性脂肪肝小鼠模型作用影响  

Effects of puerarin on a mouse model of nonalcoholic fatty liver based on the liver Dusp9-ASK1 signaling pathway

作　　者：施凯舜[1] 徐峥[1] 岳跃兵 黄洁 SHI Kaishun;XU Zheng;CHEN Yan;HUANG Jie(The Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou310005,Zhejiang,China)

机构地区：[1]浙江中医药大学附属二院,浙江杭州310005

出　　处：《实用中医内科杂志》2025年第2期105-107,I0020,I0021,共5页Journal of Practical Traditional Chinese Internal Medicine

基　　金：浙江省医药卫生科技计划项目(2021KYA586)。

摘　　要：目的探讨基于肝脏Dusp9-ASK1信号通路,葛根素影响非酒精性脂肪肝小鼠模型的机制。方法选择50只雄性小鼠进行高脂高糖造模,造模后随机分为高剂量组(PUE-H)、中剂量组(PUE-M)、低剂量组(PUE-L)、模型组(HFHC)、ASK1抑制剂组(SEL)各10只,另取10只正常小鼠做为对照组。将相应浓度的葛根素采取灌胃方法给予葛根素各组,6周后肝组织取材。分别检测6组小鼠肝组织Dusp9基因表达情况、Dusp9、p-ASK1蛋白水平以及免疫组化染色检测小鼠肝脏组织Dusp9蛋白的表达。结果(1)Dusp9基因表达在不同剂量组中均有显著提高(P<0.01),且高剂量组和中剂量组基因表达存在显著差异(P<0.01),但Dusp9基因表达在中、高剂量组并无显著差异(P>0.05)。(2)各组葛根素对Dusp9蛋白的表达较模型组有明显提高(P<0.01)。同时,Dusp9蛋白的表达随着葛根素浓度的升高而逐渐升高,表现为剂量依赖。从P-ASK1蛋白水平看,葛根素各剂量组的P-ASK1蛋白表达较模型组有明显下降,各剂量组间差异明显(P<0.01)。(3)免疫组化结果显示,葛根素各剂量组的肝脏中Dusp9蛋白与模型组相比,其表达明显提高。且3组组间均有显著性差异(P<0.05)。结论葛根素影响非酒精性脂肪肝小鼠模型的主要途径是肝脏的Dusp9-ASK1信号通路。Objective To explore the mechanism of puerarin influence on nonalcoholic fatty liver mouse model through hepatic Dusp9-ASK1 signaling pathway.Methods Fifty male mice were randomly divided into model group(HFHC),puerarin high-dose group(Pue-H),puerarin medium dose group(Pue-M),puerarin low-dose group(Pue-L),and ASK1 inhibitor group(SEL),and 10 normal mice were selected as control group.Puerarin in each group was given the corresponding concentration by intragastric administration,and the liver tissue was sampled 6 weeks later.The expression of Dusp9 gene,Dusp9 and p-ASK1 protein were detected.Results(1)The expression of Dusp9 gene in puerarin dose groups was significantly higher than that in model group(P<0.01),and the expression of Dusp9 gene in puerarin medium and high dose groups was significantly higher than that in low dose groups(P<0.01),but there was no difference between middle and high dose groups(P>0.05).(2)The expression of Dusp9 protein in puerarin groups was significantly higher than that in model group(P<0.01),and with the increase of puerarin concentration,Dusp9 protein expression increased gradually,showing dose-dependent dependence.From the perspective of P-ASK1 protein level,compared with model group,the expression of P-ASK1 protein in all puerarin dose groups was significantly decreased(P<0.01),and there were significant differences among all dose groups(P<0.01).(3)The results of immunohistochemistry showed that the expression of Dusp9 protein in liver of each puerarin dose group was significantly higher than that of model group(P<0.01).There were significant differences among the three groups(P<0.05).Conclusion Puerarin can affect the mouse model of nonalcoholic fatty liver through the Dusp9-ASK1 signaling pathway of liver.

关 键 词：葛根素 非酒精性脂肪肝 Dusp9 ASK1 

分 类 号：R285.5[医药卫生—中药学]