Zuo Xiao-Bin, Sun Xiao-Ming, Wang Chun-Yu, Liu Jing, Xiao Xiao-He, Bai Zhao-Fang
Chengde Medical University Chengde 067000,China the Fifth Medical Center of PLA General Hospital,China Military Institure of Chinese Medicine Integrative Medical Centre Beijing 100039,China.
the Fifth Medical Center of PLA General Hospital,China Military Institure of Chinese Medicine Integrative Medical Centre Beijing 100039,China Beihua University Jilin 132013,China.
Zhongguo Zhong Yao Za Zhi. 2019 Mar;44(6):1238-1245. doi: 10.19540/j.cnki.cjcmm.20181210.001.
The study was aimed to investigate the protective effect and pharmacodynamic difference of the ethanol extracts of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus on the drug-induced liver injury induced by acetaminophen.The cell activations of LO2 cells treated by Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts were tested by CCK-8 essay.The effects of ethanol extracts on cell survival rate,the activities of ALT and AST in culture medium were detected based on the injury model of LO2 cells induced by APAP.Further,in purpose to observe the protective effect of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts on a mouse model of liver injury induced by intraperitoneal injectionof acetaminophen was established.Mice were randomly divided into control group,model group,positive drug group and Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts administration groups.The activities of ALT and AST in the serum and the levels of MDA,SOD,GSH and GSH-PX in the liver homogenate of the mice were detected by commercial kits.The HEstaining was used to observe the histopathological changes of liver tissue in each group and the TUNEL staining was used to observe the hepatocyte apoptosis.The results showed that the ethanol extracts at less than 1 g·L~(-1)did not affect the activity of LO2 cell.Compared with the model group,the cell survival rates of the Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups was significantly increased;the ALT and AST in the culture medium were distinct decreased(P<0.05 or P<0.01).The survival rate of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract from different batches were similar,while that of the Schisandrea Sphenatherae Fructus ethanol extract from different batches were quite different(P<0.05or P<0.01).Further,animal experiments showed that Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups could markedly inhibit the increase of ALT and AST levels in serum(P<0.01),decrease MDA content significantly(P<0.01),and increase GSH,GSH-PX and SOD activity significantly(P<0.01).Among them,compared with other groups,Schisandrae Sphenantherae Fructus ethanol extract-2 group showed the best effect(P<0.05 or P<0.01)while Schisandrae Sphenantherae Fructus ethanol extract-1 showed a poor effect(P<0.05 or P<0.01).In conclusion,both Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts have protective effect on APAP-induced drug-induced liver injury and there was a certain difference in the efficacy between Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts from different habitats.
本研究旨在探讨南五味子果实和五味子果实乙醇提取物对乙酰氨基酚诱导的药物性肝损伤的保护作用及药效学差异。采用CCK-8法检测南五味子果实和五味子果实乙醇提取物处理的LO2细胞的细胞活性。基于APAP诱导的LO2细胞损伤模型，检测乙醇提取物对细胞存活率、培养基中ALT和AST活性的影响。此外，为观察南五味子果实和五味子果实乙醇提取物对腹腔注射乙酰氨基酚诱导的小鼠肝损伤模型的保护作用，建立了该模型。将小鼠随机分为对照组、模型组、阳性药物组和南五味子果实及五味子果实乙醇提取物给药组。采用商业试剂盒检测小鼠血清中ALT和AST活性以及肝匀浆中MDA、SOD、GSH和GSH-PX水平。采用HE染色观察各组肝组织的组织病理学变化，采用TUNEL染色观察肝细胞凋亡情况。结果显示，浓度小于1 g·L⁻¹的乙醇提取物对LO2细胞活性无影响。与模型组相比，南五味子果实和五味子果实乙醇提取物给药组的细胞存活率显著提高；培养基中ALT和AST明显降低（P<0.05或P<0.01）。不同批次的南五味子果实和五味子果实乙醇提取物的存活率相似，而不同批次的南五味子果实乙醇提取物的存活率差异较大（P<0.05或P<0.01）。此外，动物实验表明，南五味子果实和五味子果实乙醇提取物给药组可显著抑制血清中ALT和AST水平的升高（P<0.01），显著降低MDA含量（P<0.01），并显著提高GSH、GSH-PX和SOD活性（P<0.01）。其中，与其他组相比，南五味子果实乙醇提取物-2组效果最佳（P<0.05或P<0.01），而南五味子果实乙醇提取物-1组效果较差（P<0.05或P<0.01）。综上所述，南五味子果实和五味子果实乙醇提取物对APAP诱导的药物性肝损伤均有保护作用，不同产地的南五味子果实和五味子果实乙醇提取物在药效上存在一定差异。
