六味五灵片对硫代乙酰胺诱导的大鼠肝纤维化的保护作用  

Protective effects of Liuwei Wuling Tablet on hepatic fibrosis induced by thioacetamide in rats

作　　者：代炆璋 林丽 陈媛媛 丁凯欣 石伟 柏兆方 肖小河[1,2] DAI Wenzhang;LIN Li;CHEN Yuanyuan;DING Kaixin;SHI Wei;BAI Zhaofang;XIAO Xiaohe(College of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Department of Hepatology,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]中国人民解放军总医院第五医学中心肝病医学部,北京100039

出　　处：《湖南中医药大学学报》2022年第9期1413-1418,共6页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金重点项目(81930110)。

摘　　要：目的研究六味五灵片对硫代乙酰胺(thioacetamide,TAA)诱导的大鼠肝纤维化的保护作用。方法将SD大鼠随机分为对照组(N组),模型组(M组),阳性对照药扶正化瘀胶囊组(Y组),六味五灵片低、中、高剂量组(LL组、LM组、LH组)和辅料组(F组)。除N组外,其余各组采用腹腔注射3%TAA(150 mg·kg^(-1))造模。Y组(405 mg·kg^(-1))、LL组(202.5 mg·kg^(-1))、LM组(405 mg·kg^(-1))、LH组(810 mg·kg^(-1))和F组持续干预6周后检测血清谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、碱性磷酸酶(alkaline phosphatase,ALP)以及层粘连蛋白(laminin,LN)水平;RT-PCR测定肝纤维化大鼠肝组织中α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的mRNA表达量;HE、Masson、Sirius red染色观察各组大鼠肝组织病理形态学和肝组织纤维化程度。结果与N组相比,M组出现肝组织结构异常、炎性细胞浸润和胶原沉积,各项生化指标加重。与M组相比,LL组、LM组、LH组和Y组明显改善了大鼠肝组织结构异常、炎性细胞浸润和胶原沉积;显著降低了血清中肝损伤指标ALT、AST、ALP以及肝纤维化指标LN的水平(P<0.05,P<0.01,P<0.001);显著抑制了肝组织中α-SMA mRNA的表达(P<0.01);F组ALT、AST、ALP、LN水平及α-SMA mRNA的表达没有变化。结论六味五灵片对TAA诱导的大鼠肝纤维化具有一定的防治作用,其机制可能与抑制肝星状细胞的活化有关。Objective To study the protective effects of Liuwei Wuling Tablet on thioacetamide(TAA)-induced hepatic fibrosis in rats.Methods SD rats were randomly divided into control group(N group),model group(M group),positive control drug Fuzheng Huayu Capsule group(Y group),Liuwei Wuling Tablet low-dose(LL),medium-dose(LM)and high-dose(LH)groups,and the excipient group(F group).All experimental groups except the N group were intraperitoneally injected with 3%TAA(150 mg/kg)to establish the model.Y group(405 mg/kg),LL group(202.5 mg/kg),LM group(405 mg/kg),LH group(810 mg/kg),F group were continued to intervene for 6 weeks.The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP)and laminin(LN)were detected.The expression ofα-smooth muscle actin(α-SMA)mRNA in liver tissue of hepatic fibrosis rats were detected by RT-PCR.The pathomorphology and fibrosis degrees of liver tissue were observed with HE,Masson and Sirius red staining.Results Compared with the N group,the abnormal hepatic lobule structure,inflammatory cell infiltration and collagen deposition were shown and the biochemical indexes were aggravated in the M group.Compared with the M group,the abnormal hepatic lobule structure,inflammatory cell infiltration and collagen deposition were improved in LL group,LM group,LH group and Y group;the content of liver injury index ALT,AST,ALP and hepatic fibrosis index LN in serum of LL group,LM group,LH group and Y group significantly reduced(P<0.05,P<0.01,P<0.001);the expression ofα-SMA mRNA in liver tissue was significantly inhibited(P<0.01);the levels of ALT,AST,ALP,LN and the expression ofα-SMA mRNA did not change in the F group.Conclusion Liuwei Wuling Tablet has a certain preventive and therapeutic effect on TAA-induced hepatic fibrosis in rats,and its mechanism may be related to the inhibition of hepatic stellate cells activation.

关 键 词：六味五灵片 硫代乙酰胺 肝纤维化 肝星状细胞 层粘连蛋白 

分 类 号：R285.5[医药卫生—中药学]