丹参绞股蓝茶对四氯化碳所致小鼠急性肝损伤细胞炎症凋亡保护作用和机制研究  

Protective effect and mechanism of Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea on apoptosis of mice cells with acute liver injury induced by carbon tetrachloride

作　　者：谭电波[1] 刘中华 杜青 曾宏亮 李跃辉[1] TAN Dianbo;LIU Zhonghua;DU Qing;ZENG Hongliang;LI Yuehui(Hunan Province Chinese Medicine Research Institute,Changsha 410006,China;Hunan Shanyuan Biotechnology Co.,Ltd.,Yueyang 410500,China)

机构地区：[1]湖南省中医药研究院,长沙410006 [2]湖南善源生物科技有限公司,湖南岳阳410500

出　　处：《中国实验动物学报》2024年第11期1417-1423,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：湖南省中医药管理局(中医药名医名方制剂重点研究室)。

摘　　要：目的基于沉默信息调节因子1(silent information regulator 1,SIRT1)/高迁移率族蛋白B1(high mobility group protein B1,HMGB1)/核转录因子-κB(nuclear transcription factor-κB,NF-κB)信号轴探讨丹参绞股蓝茶对四氯化碳(carbon tetrachloride,CCl4)所致小鼠急性肝损伤肝细胞炎症凋亡反应的抑制作用和机制研究。方法C57BL/6小鼠随机分为正常组、模型组、白藜芦醇组、丹参绞股蓝茶低、中、高剂量组、阳性药组,连续灌胃给药14 d。采用腹腔注射0.5%CCl4橄榄油溶液(5 mL/kg)的方法建立小鼠急性肝损伤模型。生化法检测小鼠血清中丙氨酸转移酶(alanine transferase,ALT)、天冬氨酸转移酶(aspartate transferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)及肝组织羟脯氨酸(hydroxyproline,Hyp)、丙二醛(malonaldehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平;酶联免疫吸附法检测血清炎性因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-1β(interleukin-1β,IL-1β)水平;苏木素-伊红(HE)染色和TUNEL染色检测肝组织病理形态结构和肝细胞凋亡情况;Western Blot检测SIRT1、HMGB1和NF-κB蛋白表达。结果与正常组比较,模型组小鼠血清ALT、AST、LDH水平和肝组织Hyp活性显著升高,以及肝组织中MDA和SOD活性明显降低,血清炎性因子TNF-α、IL-6和IL-1β水平显著升高(P<0.05或P<0.01),肝组织存在明显的病理损伤以及肝细胞凋亡情况,肝组织中SIRT1蛋白的表达明显降低,HMGB1和NF-κB蛋白的表达升高;与模型组比较,丹参绞股蓝茶高剂量组和白藜芦醇组小鼠血清肝功能指标ALT、AST、LDH水平和肝组织Hyp活性显著降低,以及肝组织中MDA和SOD活性明显增加,血清炎性因子TNF-α、IL-6和IL-1β水平显著降低,肝组织的病理损伤以及肝细胞凋亡情况得到明显改善,肝组织中SIRT1蛋白表达增加,HMGB1和NF-κB蛋白的表达降低(P<0.05或P<0.01)。结论�Objective Use of silencing information regulatory factor 1(SIRT1)/high mobility group protein B1(HMGB1)/nuclear transcription factor-κB(NF-κB)to investigate the inhibitory effect and mechanism of Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea on hepatocyte inflammatory apoptosis in mice with carbon tetrachloride(CCl4)-induced acute liver injury.Methods C57BL/6 mice were randomly divided into a control group;model group;resveratrol group;Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea low-,medium-,and high-dose groups;and a positive drug group.The mice were given continuous intragastric administration of the treatments for 14 days.An acute liver injury model was established by intraperitoneal injection of 0.5%CCl4 olive oil solution(5 mL/kg).The levels of alanine transferase(ALT),aspartate transferase(AST),lactate dehydrogenase(LDH)in serum and hydroxyproline(Hyp),malondialdehyde(MDA),and superoxide dismutase(SOD)in the liver were determined by biochemical method.Serum levels of inflammatory tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1βwere determined by enzyme-linked immunosorbent assay.Eosin-hematoxylin and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining were used to examine the pathological morphology and apoptosis in liver tissues.The protein expression of SIRT1,HMGB1,and NF-κB were detected by Western Blot.Results Compared with those of the control group,the model group’s serum ALT,AST,and LDH levels and liver tissue Hyp activity were significantly increased;MDA and SOD activities in liver tissue were significantly decreased;the levels of inflammatory factors TNF-α,IL-6,and IL-1βin liver tissue were significantly increased;and there were obvious signs of pathological injury and hepatocyte apoptosis in the liver tissue.The expression of SIRT1 protein decreased significantly,while the expression of HMGB1 and NF-κB proteins increased,in liver tissue.Compared with those of the model group,the Salvia miltiorrhiza Bunge gynostemma

关 键 词：急性肝损伤 炎性凋亡 沉默信息调节因子1 高迁移率族蛋白B1 核转录因子-κB 

分 类 号：Q95-33[生物学—动物学]