柴胡皂苷b1缓解CCl_(4)诱导急性肝损伤的作用机制研究

Action Mechanism of SSb1 in Alleviating CCl_(4)-Induced Acute Liver Injury

目的:研究柴胡皂苷b1(SSb1)对CCl_(4)诱导急性肝损伤的保护作用。方法:将雄性C57BL/6小鼠按体质量随机分为空白组、模型组、阳性药组(联苯双酯,150 mg/kg)、SSb1低剂量组(SSb1-L,2.5 mg/kg)和SSb1高剂量组(SSb1-H,10 mg/kg),每组8只。阳性药组每天灌胃给药;SSb1-L和SSb1-H组每天腹腔注射给药,每日1次,连续给药7 d;空白组和模型组小鼠给予等体积的生理盐水。第7天给药1 h后,除空白组外,其余各组小鼠腹腔注射0.2%CCl_(4)橄榄油(10 mL/kg)诱导复制急性肝损伤小鼠模型。造模17 h后,收集血清和肝组织。检测小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、白细胞介素-6(IL-6)、IL-1β和肿瘤坏死因子-α(TNF-α)的水平,测定小鼠肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)以及相关炎症因子IL-6、IL-1β、TNF-α的水平,检测小鼠肝组织中IL-6、IL-1β、TNF-α、核转录因子E2相关因子(Nrf2)和血红素加氧酶-1(HO-1)基因的表达水平。结果:SSb1可显著降低急性肝损伤小鼠的肝脏指数,减轻肝组织病理损伤,降低急性肝损伤小鼠血清中ALT、AST、IL-6、IL-1β及TNF-α水平。SSb1也可抑制肝组织中相关炎症因子的表达,调节MDA和SOD的活性,调控炎症因子和氧化应激相关基因的转录。结论:SSb1可能通过调节炎症和氧化应激反应从而发挥对急性肝损伤小鼠的保护作用。

Objective:To study the protective effect of saikosaponin b1(SSb1)on CCl_(4)-induced acute liver injury.Methods:Male C57BL/6 mice were randomly divided into the blank group,the model group,the positive drug group(Bifendate,150 mg/kg),the SSb1-L group(2.5 mg/kg)and the SSb1-H group(10 mg/kg)according to body weight,with 8 mice in each group.The positive drug was intervened by gavage every day,and the SSb1 groups were intervened by intraperitoneal injection once a day for 7 days.The blank group and the model group were given the same volume of normal saline.One hour after administration on the 7th day,except the blank group,the mice in other groups were intraperitoneally injected with 0.2%CCl_(4)olive oil(10 mL/kg)to induce acute liver injury.After 17 hours of modeling,serum and liver tissues were collected in mice.The serum levels of ALT,AST,IL-6,IL-1βand TNF-αwere detected,and the expressions of SOD,MDA and related inflammatory factors of IL-6,IL-1βand TNF-αin liver tissues were determined,and the gene expressions of IL-6,IL-1β,TNF-α,Nrf2 and HO-1 in liver tissues were measured in the groups.Results:SSb1 could significantly reduce the liver indexes,alleviate the pathological damage of liver tissues,and reduce serum levels of ALT,AST,IL-6,IL-1βand TNF-αin mice with acute liver injury.SSb1 could also inhibit the expressions of related inflammatory factors in liver tissues,improve the activities of MDA and SOD,and regulate the transcription of inflammatory factors and oxidative stress-related genes.Conclusion:SSb1 might play a protective role in mice with acute liver injury by regulating inflammation and oxidative stress.