黄芪总皂苷对CCl_4诱导急性肝损伤小鼠保护作用及机制初探

Protective Effects and Mechanism of Astragalus Total Saponins on CCl_4-induced Acute Hepatic Injury in Mice

目的:探讨黄芪总皂苷对四氯化碳(CCl_4)诱导的小鼠急性肝损伤的保护作用及机制研究。方法:将60只小鼠随机分为正常组、模型组、黄芪总皂苷200、100、50mg/kg组、联苯双酯150mg/kg组,每组10只,正常组和模型组灌服等量溶媒,每天1次,连续10天。末次给药后,每只小鼠按10 ml/kg剂量腹腔注射5%CCl_4橄榄油溶液。16～18 h后,经眼球取血,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性;肝脏匀浆后检测肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)活性; HE染色观察肝脏组织病理形态学的改变; RT-qPCR技术检测肝脏组织IL-1和TNF-αmRNA的表达; Western blot技术检测肝脏组织IL-1和TNF-α蛋白的相对表达。结果:与正常组相比,模型组小鼠血清ALT、AST、MDA活性显著升高,SOD活性显著降低;与模型组比较,黄芪总皂苷200、100、50mg/kg组ALT、AST、MDA活性出现不同程度的降低,SOD活性显著升高;肝脏组织形态结构改变明显减轻,RT-qPCR和Western blot结果显示肝脏组织IL-1和TNF-α相对表达明显降低。结论:黄芪总皂苷对CCl_4致小鼠急性肝损伤有显著保护作用,其机制可能与减轻肝细胞凋亡,抑制炎症因子释放有关。

Objective: To investigate the protective effect and mechanism of Astragalus total saponins on acute liver injury induced by carbon tetrachloride( CCl4) in mice. Methods: 60 mice were randomly divided into the control group,the model group,high,medium and low doses of Astragalus total saponins group( 200,100,50 mg/Kg) and bifendate group( 150 mg/kg),10 mice in each group. Animals were administered for constantly 10 days,once per day,while mice in the control group and the model group were given the same amount of solvent. After the last administration,5% CCl4 olive oil solution at dose of 10 ml/kg was intraperitoneally injected. 16 ~ 18 hours later,mice eyeballs were taken to determine the serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST). Liver homogenate was observed to detect malondialdehyde( MDA) and superoxide dismutase( SOD) content. The pathological changes of liver tissues were observed by HE staining. The expressions of IL-1 and TNF-α mRNA and protein in liver tissues were detected by RT-qPCR and Western blot. Results: Compared with the control group,the levels of ALT,AST,MDA in the model group were significantly increased,and its SOD level was significantly decreased( P < 0. 01). Compared with the model group,levels of ALT,AST and MDA in Astragalus total saponins group( 200,100,50mg/kg) were decreased,while SOD was significantly increased( P < 0. 01). The morphological changes of liver tissues were significantly reduced. The relative expressions of IL-1 and TNF-α in liver tissues were significantly decreased in RT-qPCR and Western blot.Conclusion: Astragalus total saponins can significantly protect mice from acute liver injury induced by CCl4. The mechanism may be related to the reduction of hepatocyte apoptosis and the inhibition of the release of inflammatory cytokines.