摘要
目的:探讨大黄对重剂蜈蚣给药小鼠的肝脏保护作用机制。方法:以10倍剂量(6.5 g·kg^(-1)·d^(-1))蜈蚣提取物灌胃小鼠为模型,设置模型组、大黄干预组1(49 mg·kg^(-1)·d^(-1))、大黄干预组2(98 mg·kg^(-1)·d^(-1)),同时设置正常组。持续给药28 d,禁食24 h时观察小鼠肝脏组织形态学变化,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及碱性磷酸酶(ALP)含量,免疫荧光检测肝细胞核因子E2相关因子2(Nrf2)表达及入核情况,WesternBlot测定组织醌氧化还原酶(NQ O1)和血红素氧化酶-1(H O-1)蛋白表达。结果:10倍剂量蜈蚣给药小鼠出现肝索结构模糊和细胞排列紊乱、水肿以及部分坏死,血清ALT、AST、ALP含量显著升高(P<0.05)。与模型组比较,大黄干预后可减轻病理形态学改变,显著降低血清ALT、AST、ALP含量(P<0.05),免疫荧光显示大黄干预两组肝细胞核内Nrf2表达增加,Western Blot显示大黄干预组1肝组织NQO1、HO-1蛋白表达显著升高(P<0.05)。结论:低剂量大黄即可改善重剂蜈蚣给药造成小鼠肝脏组织细胞损伤、稳定肝功能相关指标,激活Nrf2/ARE氧化应激通路并增强下游NQO1、HO-1蛋白表达,是其发挥肝脏保护机制之一。
Objective:To investigate the mechanism of hepatoprotective effect of Rhei Radix Et Rhizoma on mice administered with heavy doses of Scolopendra.Methods:Ten times the dose of Scolopendra extract gavaged mice(6.5 g·kg-1·d-1)were used to make a model,and randomly divided into model group,Rhei Radix Et Rhizoma intervention group 1(49 mg·kg-1·d-1),Rhei Radix Et Rhizoma intervention group 2(98 mg·kg-1·d-1),and normal control group were set up.The histomorphological changes of liver of mice were observed after 28 d of continuous administration and 24 h of fasting,and the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alkaline phosphatase(ALP)were measured.Immunofluorescence detection of nuclear factor E2-related factor 2(Nrf2)expression and nuclear entry in hepatocytes,and Western Blot determination of tissue NAD(P)H:quinone oxidoreductase 1(NQO1)and heme oxygenase-1(HO-1)protein expression.Results:Ten-fold doses of Scolopendra administered to mice showed blurred hepatic cord structure and disorganized cell arrangement,edema,and partial necrosis,and elevated serum ALT,AST,ALP level(P<0.05).Compared with the model group,Rhei Radix Et Rhizoma intervention reduced the pathomorphological changes and significantly decreased the serum ALT,AST and ALP levels(P<0.05).Immunofluorescence showed that the expression of Nrf2 increased in the nucleus of hepatocytes in the two groups of Rhei Radix Et Rhizoma intervention,and Western Blot showed that the expression of NQO1 and HO-1 proteins in hepatocytes of hepatocytes of hepatocytes of the Rhei Radix Et Rhizoma intervention group 1 tissue was significantly elevated(P<0.05).Conclusion:Low dose of Rhei Radix Et Rhizoma can improve the liver tissue cell injury and stabilize the liver function related indexes in mice caused by heavy dose of Scolopendre administration,and the activation of Nrf2/ARE oxidative stress pathway and enhancement of downstream NQO1 and HO-1 protein expression is one of its hepatoprotective mechanisms.
作者
冯婷
黄羚
张振
胡玉星
易纯
王艺
刘梦思
陈雅婷
田莎
黄晓蒂
田雪飞
FENG Ting;HUANG Ling;ZHANG Zhen;HU Yuxing;YI Chun;WANG Yi;LIU Mengsi;CHEN Yating;TIAN Sha;HUANG Xiaodi;TIAN Xuefei(School of Integrative Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Key Laboratory of Chinese Medicine Oncology in Hunan Provincial Universities,Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Provincial Key Laboratory of Translational Medicine in Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Medical School,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2023年第9期4387-4391,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(No.82074450)
湖南省自然科学基金面上项目(No.2020JJ4066)
湖南省教育厅重点项目(No.21A0243)
湖南省教育厅青年项目(No.21B0384)。
