南、北五味子醇提物对对乙酰氨基酚诱导的药物性肝损伤保护作用及药效差异研究

探究南、北五味子醇提物对对乙酰氨基酚(APAP)诱导的药物性肝损伤保护作用及差异。CCK-8法检测南、北五味子醇提物对LO2细胞生存率的影响;构建APAP诱导的LO2细胞损伤模型,检测南、北五味子醇提物对细胞损伤的影响;利用APAP构建小鼠肝损伤模型并将小鼠随机分为对照组、模型组、阳性药组及不同批次南、北五味子醇提物组,通过小鼠血清ALT,AST检测,肝组织中的MDA,GSH,GSH-PX和SOD含量测定,HE染色以及TUNEL染色等评价不同批次南、北五味子醇提物对药物性肝损伤的保护作用。结果显示,醇提物剂量小于1 g·L^-1时不影响LO2细胞生存率。与模型组相比,南、北五味子醇提物各组均可显著抑制APAP诱导的肝细胞凋亡,提高细胞生存率,同时显著降低细胞培养上清中ALT,AST水平(P<0.05或P<0.01)。且北五味子醇提物各组生存率较为一致,而南五味子醇提物不同组之间生存率差异较大。利用APAP诱导的小鼠肝损伤模型研究表明,与模型组相比,南、北五味子醇提物各组均能够明显改善病理损伤,抑制细胞凋亡和血清中ALT和AST水平升高(P<0.01),降低MDA含量(P<0.01),同时显著提高GSH,GSH-PX和SOD活性(P<0.01),其中南五味子醇提物-2组作用最佳(P<0.05或P<0.01)。与其他给药组相比,南五味子醇提物-1作用则较差(P<0.05或P<0.01)。该研究表明南、北五味子醇提物对APAP诱导的药物性肝损伤均有保护作用但不同产地南五味子作用差异较大。

Investigation on protective effect and efficacy difference of extract of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus against acetaminophen-induced liver injury

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.