蒙药古日古木-13对CCl_(4)诱导的大鼠肝纤维化的改善作用及其机制研究  

Study on Mechanism of Mongolian Medicine Gurigumu-13 of CCl_(4)-Induced Hepatic Fibrosis in Rats

作　　者：道力格玛 邓乌力吉 萨础拉[1] 萨日呼 陈圆圆 宝特力格尔 包套格申 Daoligema;Deng Wuliji;Sachula;Sarihu;Chen Yu uanyuan;Bao Teligeer;Bao Taogeshen(Inner Mongolia Medical University,Hohhot 010110,China;The People's Hospital Affiliated to Inner Mongolia Medical University,Hohhot 010020,China)

机构地区：[1]内蒙古医科大学,内蒙古呼和浩特010110 [2]内蒙古医科大学附属人民医院,内蒙古呼和浩特010020

出　　处：《亚太传统医药》2022年第11期19-23,共5页Asia-Pacific Traditional Medicine

基　　金：内蒙古自治区蒙医药协同创新培育中心研究项目(MYYXT201901)。

摘　　要：目的:探讨蒙药古日古木-13对CCl_(4)诱导的大鼠肝纤维化的改善作用,并阐明其改善肝纤维化的可能机制。方法:将60只SD大鼠随机分为空白对照组、阳性对照组、模型对照组和古日古木-13低、中、高剂量组。除空白组外,其余各组腹腔注射CCl_(4)诱导肝纤维化7周,从第4周开始,各组灌胃给予相应剂量的治疗药物。末次给药后,采集大鼠血液和肝脏组织以备检测。采用HE染色观察大鼠肝脏组织形态学变化;应用生化检测测定大鼠血清ALT、AST;采用ELISA法测定大鼠血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原氨基端原肽(PⅢNP)表达量;采用实时荧光定量PCR技术和免疫组织化学反应分别检测大鼠肝脏组织转化生长因子(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达量。结果:与空白组比较,模型组大鼠血清ALT、AST水平显著升高(P<0.05);血清HA、LN、PⅢNP,肝组织TGF-β和α-SMA蛋白水平显著升高(P<0.01)。与模型组比较,古日古木-13低、高剂量组大鼠血清HA显著降低(P<0.01),古日古木-13低、中剂量组血清LN显著降低(P<0.05),古日古木-13各剂量组大鼠血清PⅢNP含量显著降低(P<0.05),古日古木-13高剂量组大鼠肝组织TGF-β1显著降低(P<0.01),古日古木-13各剂量组大鼠肝组织α-SMA水平显著降低(P<0.05)。结论:蒙药古日古木-13对肝纤维化有明显的抑制作用,其机制可能是通过作用于肝星状细胞,抑制肝组织α-SMA的表达,阻断肝星状细胞的活化,进而抑制肝星状细胞自分泌TGF-β1,并且使胶原蛋白的合成减少,缓解细胞外基质的过度沉积,从而发挥改善肝纤维化的作用。Objective:To explore the ameliorative effect of Mongolian medicine Gurigumu-13on CCl_(4)-induced hepatic fibrosis in rats and to elucidate the possible mechanism of Gurigumu-13in improving hepatic fibrosis.Methods:60SD rats were randomLy divided into normal group,model group,positive control group,Gurigumu-13low,middle and high dose groups.Except the normal group,the other groups were injected intraperitoneally with CCl_(4) to induce liver fibrosis for 7weeks.From the 4th week,each group was given corresponding dose of therapeutic drugs by intragastric administration.After the last administration,blood was taken and liver tissue was collected.The morphological changes of liver tissue were observed by HE staining;The serum ALT and AST were determined by biochemical detection;The level of serum hyaluronic acid(HA),laminin(LN),and N-terminal procollagenⅢ propeptide type(PⅢNP)were determined by Elisa method;The transforming growth factor-β1(TGF-β1)was determined by real-time fluorescence quantitative PCR;The expression ofα-smooth muscle actin(α-SMA)was detected by immunohistochemistry.Results:Compared with the normal group,the serum levels of ALT and AST in the model group significantly increased(P<0.05),and the serum levels of HA,LN,PⅢNP,the expression of TGF-β1andα-SMA in liver tissue were significantly increased(P<0.01).Compared with the model group,the serum HA of rats in the low and high dose groups of Gurigumu-13decreased significantly(P<0.01),the serum LN in the low and medium dose groups of Gurigumu-13decreased significantly(P<0.05),and the content of PⅢNP in serum of each dose group of Gurigumu-13groups decreased significantly(P<0.05).The content of TGF-β1in liver tissue decreased significantly in Gurigumu-13high dose group(P<0.01).Each dose group of Gurigumu-13significantly reduced the level ofα-SMA in liver tissue of rats with liver fibrosis(P<0.05).Conclusion:The Mongolian medicine Gurigumu-13has obvious inhibitory effect on liver fibrosis,and its mechanism may act on hepatic stellate cell

关 键 词：蒙药古日古木-13 肝纤维化 作用机制 肝星状细胞 

分 类 号：R285.5[医药卫生—中药学] R29[医药卫生—中医学]