双虎清肝颗粒对四氯化碳诱发大鼠肝损伤模型肝组织基因表达谱的影响

Effects of Shuanghu qinggan granule on gene expression in liver injury induced by carbon tetrachloride in rats

目的探讨双虎清肝颗粒对四氯化碳诱发大鼠肝损伤模型肝组织基因表达谱的影响。方法清洁级Sprague-Daw ley大鼠60只,随机均分为6组。除正常对照组外,均皮下注射40%四氯化碳8周,各治疗组再给予不同剂量双虎清肝颗粒干预8周;水飞蓟素对照组给予水飞蓟素干预8周,观察干预前后6组大鼠肝脏组织基因表达谱的变化。结果A组大鼠各基因表达无明显变化。四氯化碳干预后B、C1、C2、C3、D组与A组相比,表达下调的基因有:CY相关基因、脂代谢相关基因、蛋白质糖基化相关基因;表达上调的基因有:与细胞周期和细胞凋亡相关的基因、与脂转运相关基因、参与细胞黏附、细胞连接和胶原形成的基因。双虎清肝颗粒干预后C1、C2、C3、D组与B组比较,CY相关基因、蛋白质糖基化相关基因、脂代谢相关基因的表达均上调;双虎清肝颗粒干预前后C1、C2、C3组间比较,干预前上调者干预后下调明显,干预前下调者干预后上调明显,且随着双虎清肝颗粒剂量的增加,基因表达的幅度也增加。双虎清肝颗粒干预后C1、C2、C3组与D组比较,其基因表达的改变和双虎清肝颗粒导致的基因表达改变不同(有下调、有无变化、也有上调)。结论双虎清肝颗粒能够从基因水平减轻四氯化碳所诱发的肝脏损伤,并且量效关系明显。

Objective To investigate the effects of Shuanghu qinggan granule on gene expression in liver injury induced by carbon tetrachloride in rats. Methods Sixty Sprague-Dawley rats were divided into 6 groups, namely normal control group （A）, model group （B）, Shuanghu qinggan granule low （C1）, medium （C2）, high （C3） dose group and silymarin positive contrast group （D）. The rats of group B, C1, C2, C3 and D were subcutaneously injected by carbon tetrachloride （3 mL/kg body weight） twice a week for 8 weeks. The rats of group C1 , C2, C3 were then administered with Shuanghu qinggan granule at the doses of 5 g/kg body weight （ C3 ）, 2.5 mg/kg body weight （ C2）, 1.2 g/ kg body weight （ C 1 ） for 8 weeks. The rats of group D were then administered with silymarin at a dose of 50 mg/kg body weight. The changes of some gene expression were detected by gene chip techonology. Results After the intervention, the rats in group A had no significant changes in gene expression. Compared with group A, the reduced expression of the genes of rats of group B, C1, C2, C3, D were as follows after the intervention of carbon tetrachloride： CY-related genes, lipid metabolism related genes, protein glyeosylation-related genes; the up-regulated expression of the genes of rats of group B, C1 , C2, C3, D were as follows ： the cell cycle and apoptosis-related genes, fat transfer related genes, involved in cell adhesion and cell connections and the formation of collagen genes. Compared with group B, the following genes of rats of group C1 , C2, C3, D were up-regulated after the intervention of Shuanghu qinggan granule： CY-related genes, protein glycosylation-related genes, lipid metabolism related genes. Before and after the intervention of Shuanghu qinggan granule, gene expressions of rats of group C1, C2, C3 up-regulated compared to pre-intervention when they were down-regulated, down-regulated compared to pre-intervention when they were up-regulated. Involved in cell adhesion and cell connection and the formation of collagen gene. The cell cycle and apoptosis-related genes appeared to interfere with the most of the changes in gene expression also increased. The changes of gene expression in rats caused by Shuanghu qinggan granule was different from those caused by silymarin （some down-regulated, some no change, some up-regulated）. Conclusion Shuanghu qinggan granule could have the potential to relieve liver injury caused by carbon tetraehloride through genetic pathways with a remarkable dose-response correlation.