十二味穿甲片原料抗CCl4所致大鼠肝纤维化的实验研究

目的:探讨十二味穿甲片原料对四氯化碳(CCl₄)所致大鼠肝纤维化的保护作用。方法:将雄性SPF级SD 大鼠98只随机分为空白对照组,模型对照组,阳性对照组,中药十二味穿甲片原料4.2,2.8,1.4,0.7 g·kg^-1剂量组。除空白对照组腹腔注射同体积的注射用大豆油外,其余各组均腹腔注射40%的CCl₄大豆油溶液2 mL·kg^-1,每周2次并连续8周建立大鼠肝纤维化模型,造模同时给药进行抗肝纤维化干预,共59 d。通过测定体质量,检测肝功能指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB),比色法测定肝脏羟脯氨酸(Hyp)含量并进行肝内胶原定量分析,HE染色以观察肝组织病理变化,评价药物的抗纤维化作用。结果:与模型对照组比较,十二味穿甲片原料药粉4.2,2.8 g·kg^-1剂量组大鼠肝脏Hyp和胶原含量显著降低(P<0.05),2.8,0.7 g·kg^-1剂量组大鼠血清ALT、AST含量及1.4 g·kg^-1剂量组血清ALT均显著下降,差异具有显著性意义(P<0.05或P<0.01),而4.2 g·kg^-1剂量组血清ALT、AST和1.4 g·kg^-1剂量组AST含量亦呈下降趋势,但无显著性差异(P>0.05)。2.8 g·kg^-1剂量组大鼠血清ALB和TP呈明显升高趋势,但较模型对照组统计学意义不显著(P>0.05),病理结果显示2.8 g·kg^-1剂量组大鼠肝纤维化改善显著。结论:本实验条件下,十二味穿甲片原料具有抗CCl₄所致大鼠肝纤维化的作用,以2.8 g·kg^-1剂量抗肝纤维化作用最为明显。

Effects of Shierweichuanjia tablets against rats liver fibrosis induced by CCl4

OBJECTIVE To investigate protective effects of Shierweichuanjia tablets against liver fibrosis induced by carbon tetrachloride in rats.METHODS A total of 98 SD rats were randomly divided into normal control group, model control group, positive control group (colchicine tablets 0.1 mg·kg^-1) and 4 different dose groups (4.2, 2.8, 1.4, 0.7 g·kg^-1) of Shierweichuanjia tablets. Animals in normal control group were injected with the same volume of soybean oil, and animals in remaining groups were injected with mixture of 40% CCl₄ and soybean oil (2 mL·kg^-1) two times a week for eight weeks to establish liver fibrosis model in rat. Meantime, all rats were intragastrically administrated with the corresponding medicines for 59 days. Effects of drugs were observed by calculating body weight, detecting liver functions including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total protein (TP), albumin (ALB), and observing the extent of liver fibrosis. The content of Hyp in liver was determined by colorimetric method, and collagens of rat with liver fibrosis were quantitatively analyzed. HE staining was used to observe pathological changes of liver tissues, and to evaluate the anti fibrosis effects of drugs.RESULTS Compared with model control group, 4.2 and 2.8 g·kg^-1 dose groups of Shierweichuanjia tablets had significantly decreased contents of Hyp and collagens (P<0.05), 2.8 and 0.7 g·kg^-1 dose groups had significantly decreased levels of serum ALT and AST. ALT also decreased in 1.4 g·kg^-1dose group. All these differences were significant (P<0.05 or P<0.01). However, levels of ALT and AST in 4.2 g·kg^-1 dose group had a tendency to decrease, and level of AST in 1.4 g·kg^-1 dose group also decreased, but without no significant difference (P>0.05). Serum ALB and TP in 2.8 g·kg^-1 dose group were significantly higher than those in model control group, but without significant difference (P>0.05). Pathological results showed that 2.8 g·kg^-1 dose group had liver fibrosis significantly alleviated.CONCLUSION In this experiment, Shierweichuanjia tablets have protective effects against liver fibrosis induced by carbon tetrachloride, and the effect is most significant inf 2.8 g·kg^-1 dose group.