肝纤溶颗粒与复方鳖甲软肝片对大鼠肝纤维化模型细胞凋亡及内质网应激相关因子表达影响研究

Effect of Hepatic Fibrinolysis Granules combined with Fufang Biejia Ruangan Tablets on apoptosis and endoplasmic reticulum related factor expressions in rat hepatic fibrosis model

摘要:

探究肝纤溶颗粒与复方鳖甲软肝片对大鼠肝纤维化模型细胞凋亡及内质网应激相关因子表达影响。方法48 只雄性清洁级SD 大鼠随机分为：正常对照组、模型对照组、复方鳖甲软肝片组及肝纤溶颗粒组，每组各12 只。除正常对照组外各组复制肝纤维化模型。于复制模型后的3 周各组大鼠同时给药，正常对照组与模型对照组大鼠给予生理盐水1.5 ml/kg 灌胃，1 次/d；复方鳖甲软肝片组给予33.3%复方鳖甲软肝片溶液1.5 ml/kg 重灌胃，1 次/d；肝纤溶颗粒组给予33.3%肝纤溶颗粒溶液1.5 ml/kg灌胃，1 次/d。各组连续用药6 周。实验开始后第3、6 和9 周对各组大鼠肝脏病理学、细胞凋亡数量、肝纤维化指标水平以及内质网应激相关指标进行检测。结果与其他各组相比，肝纤溶颗粒组纤维增生程度评分下降（ p<0.05），肝凋亡数下降（ p<0.05）；透明质酸、层黏连蛋白、血清Ⅲ型前胶原、血清Ⅳ型胶原水平下降（p <0.05）；CHOP、ATF6 蛋白表达水平下降（ p<0.05）。结论肝纤溶颗粒组肝纤维化大鼠细胞凋亡数量和肝纤维化水平较复方鳖甲软肝片组下降，差异有统计学意义（ p<0.05），肝纤溶颗粒能够改善肝脏病理变化，调节内质网应激相关指标，对临床有指导意义。

Abstract:

To investigate the effects of Hepatic Fibrinolysis Granules combined with Fufang Biejia Ruangan Tablets on cell apoptosis and endoplasmic reticulum (ER) related factor expressions in rat hepatic fibrosis model. Methods A total of 48 male SD rats of clean grade were randomly divided into normal control group, model control group, Biejia Ruangan Tablets group and Hepatic Fibrinolysis Granules group with 12 rats in each group. The hepatic fibrosis models were copied in all the groups except the normal control group. After the model was made for 3 weeks, the rats were given medicines at the same time. In the normal control group and the model control group the rats were given intragastric administration of 1.5 ml/kg normal saline, once a day. In the Fufang Biejia Ruangan Tablets group the rats were given 33.3% Fufang Biejia Ruangan Tablets solution 1.5 ml/kg for gavage, once a day. In the Hepatic Fibrinolysis Granules group the rats were given 33.3% Hepatic Fibrinolysis solution 1.5 ml/kg for gavage, once a day. The medication continued for 6 weeks. In the 3rd, 6th and 9th week of the experiment, the liver pathology was observed, the number of apoptosis cells and the levels of hepatic fibrosis indexes and ER-related indexes were detected in all the groups. Results Compared with other groups, the fibrosis grade score significantly decreased ( p<0.05); the number of apoptotic hepatocytes was significantly reduced (p < 0.05); the levels of hyaluronic acid, laminin, serum type III procollagen and type IV collagen were decreased significantly (p < 0.05); CHOP and ATF6 expression levels also decreased significantly ( p< 0.05) in the Hepatic Fibrinolysis Granules group. Conclusions Hepatic Fibrinolysis Granules decrease the number of apoptosis cells and hepatic fibrosis level in rats with hepatic fibrosis. They are better than Biejia Ruangan Tablets in improvement of the pathological changes of liver and adjustment of endoplasmic reticulum related indicators, therefore have clinical significance.