金线莲苷对二乙基亚硝胺致小鼠肝损伤的保护作用及PELP1/ERK通路的影响

The Protective Effect of Kinsenoside on Diethylnitrosamine-Induced Hepatic Injury in Mice and the Role of PELP1/ERK Pathway in it

目的探讨金线莲苷(KS)对二乙基亚硝胺(DEN)诱导小鼠肝损伤的保护作用以及PELP1/ERK通路参与作用的分子机制。方法24只雄性C57BL/6小鼠,随机分为Control组、DEN组和KS组,每组8只。石蜡切片和HE染色检查肝脏组织病理学变化;可见分光光度法检测各组小鼠血清中ALT、AST和ALP的含量;qPCR、Western blot分别检测肝脏组织PELP1、ERK mRNA及蛋白表达水平;EL1SA测定肝脏组织TNF-α、IL-1β和IL-6的浓度。结果与对照组比较,DEN组小鼠肝脏表面粗糙、颜色变深、质地变硬,肝脏组织正常结构被破坏,血清ALT、AST和ALP含量明显升高(P<0.05),肝脏组织PELP1、ERK mRNA及蛋白表达水平显著升高(P<0.05),TNF-α、IL-1β和IL-6浓度均显著升高(P<0.05);与DEN组比较,KS组小鼠肝脏形态及细胞损伤性变化明显减轻,血清ALT、AST和ALP含量明显降低(P<0.05),肝脏组织PELP1、ERK mRNA及蛋白表达水平显著降低(P<0.05),TNF-α、IL-1β和IL-6浓度均显著降低(P<0.05)。结论金线莲苷对DEN诱导的小鼠肝损伤有显著保护作用,其机制与下调PELP1表达,阻断ERK通路活化,进而抑制炎症反应有关。

Objective To investigate the protective effect of Kinsenoside(KS)on diethylnitrosamine(DEN)-induced hepatic injury in mice and the molecular mechanism of PELP1/ERK pathway involvement.Methods Twenty-four male C57BL/6 mice were randomly divided into Control group,DEN group and KS group,with 8 mice in each group.Paraffin sections and HE staining were used to examine the pathological changes of liver tissue;the contents of ALT,AST and ALP in serum of mice in each group were detected by visible spectrophotometry;qPCR and Western blot were used to detect the mRNA and protein expression levels of PELP1 and ERK in liver tissue,respectively;EL1SA was used to determine the concentrations of TNF-α,IL-1βand IL-6 in liver tissue.Results Compared with the control group,the liver surface of the DEN group was rough,the color became darker,the texture was hardened,the normal structure of the liver tissue was destroyed,the serum ALT,AST and ALP contents,the liver tissue PELP1,AST and ALP,the expression levels of ERK mRNA and protein,and the concentrations of TNF-α,IL-1βand IL-6 were all significantly increased(P<0.05).Compared with the DEN group,the changes of liver morphology and cell damage in the KS group,the serum ALT,AST and ALP contents,the mRNA and protein expression levels of PELP1 and ERK in liver tissue,and the concentrations of TNF-α,IL-1βand IL-6 were all significantly decreased(P<0.05).Conclusion Kinsenoside has a significant protective effect on diethylnitrosamine-induced hepatic injury in mice,and its mechanism is related to down-regulating the expression of PELP1,blocking the activation of the ERK pathway,and then inhibiting the inflammatory response.