马齿苋多糖抗CCl4诱导的小鼠慢性肝纤维化作用  

Effect of purslane polysaccharides on chronic hepatic fibrosis induced by CCl4 in mice

作　　者：李小花 曹性玲[2] 刘四君[3] 曹思 钟桂香 黎晓[2] 吴丽珍[2] LI Xiao-hua;CAO Xing-ling;LIU Si-jun;CAO Si;ZHONG Gui-xiang;LI Xiao;WU Li-zhen(Asset Management Department of Gannan Medical University;School of Basic Medicine,Gannan Medical University;The First Affiliated Hospital of Gannan Medical University;Academic Affairs Office of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院资产管理处 [2]赣南医学院基础医学院 [3]赣南医学院第一附属医院 [4]赣南医学院教务处,江西赣州341000

出　　处：《赣南医学院学报》2023年第4期365-370,共6页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：江西省教育厅科学技术研究项目(GJJ180798)。

摘　　要：目的:研究马齿苋多糖(Purslane polysaccharide,POP)对小鼠慢性肝纤维化的逆转作用。方法:采用四氯化碳(CCl4)诱导的小鼠肝纤维化模型,分别灌胃给予不同剂量的POP(25、50、100 mg·kg^(-1))、2.5 mg·kg^(-1)的联苯双酯或等体积的生理盐水治疗6周。HE染色观察肝组织形态,电镜观察肝细胞结构变化,定量PCR(qPCR)方法检测肝组织中胶原蛋白(Collagen)Ⅰ和Ⅲ、α-平滑肌动蛋白(Alpha smooth muscle actin,α-SMA)、转化生长因子β1(Transforming growth factor,TGF-β1)、Smad4的mRNA表达,ELISA方法检测透明质酸(Hyaluronic acid,HA)、层黏连蛋LN(Laminin,LN)和Ⅲ型前胶原-N(Procollagen typeⅢ-N,PⅢNP)等肝纤维化相关蛋白含量,Western blot方法检测α-SMA蛋白表达。结果:(1)模型组小鼠表现为肝组织脂肪变性,空泡,脉管区炎性细胞浸润,肝细胞变性坏死,纤维增生;不同剂量POP组肝组织炎症浸润不同程度改善,肝索排列规律;(2)模型组肝细胞结构不清,细胞核增大,常染色质数量异常增加,线粒体和内质网等细胞器代偿性增多,脊增多或断裂,有少许空泡;与模型组相比,POP给药组和联苯双酯组上述状态减轻;(3)模型组α-SMA、TGF-β1、Smad4、CollagenⅢ的mRNA表达增高,POP治疗组以上基因表达呈剂量依赖性下降;(4)模型组LN、HA、PⅢNP和α-SMA含量升高,POP治疗后以上相关蛋白随剂量表达下降。结论:POP可缓解CCl4诱导的小鼠肝纤维化,其机制可能与POP抑制TGF-β1/Smad信号通路,进而下调胶原蛋白的表达有关。Objective:To study the reversal effect of purslane polysaccharide(POP)on chronic hepatic fibrosis in mice.Methods:The carbon tetrachloride(CCl4)-induced mouse liver fibrosis model was used,and different doses of POP(25,50,100 mg·kg^(-1)),2.5 mg·kg^(-1) bifendate or equal volume of normal saline were given by gavage for six weeks.The morphology of liver tissue was observed by HE staining,and the changes of hepatocyte structure were observed by electron microscope.The mRNA expressions of collagen I andⅢ,alpha smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and Smad4 in liver tissue were detected by quantitative PCR(qPCR).Hyaluronic acid,laminin(LN)and procollagen typeⅢ-N(PⅢNP)were detected by ELISA andα-SMA protein expression was detected by Western blot.Results:(1)The liver tissue of model group mice showed steatosis,vacuolation,infiltration of inflammatory cells in the vascular area,degeneration and necrosis of liver cells,and fibrosis.The inflammatory infiltrations in liver tissue of POP treatment groups were improved in varying degrees along with hepatic cord arrangement.(2)Hepatocytes of model group mice showed that the structure of cells was unclear,nucleus were enlarged,the number of euchromatin were increased abnormally,the mitochondria,endoplasmic reticulum and other organelles compensatory increased,ridges increased or broken,and a few vacuoles were found.The above phenomena were alleviated by treating with different dose of POP.(3)The mRNA expressions ofα-SMA,TGF-β1,Smad4 and CollagenⅢin the liver tissue of model group mice increased,which decreased by administering with POP in a dose-dependent manner.(4)The content of LN,HA,PIIINP in serum andα-SMA protein in the liver tissue of model group mice increased,which decreased by treating with POP.Conclusion:POP can alleviate CCl4-induced liver fibrosis in mice by inhibiting TGF-β1/Smad signaling pathway and restraining collagen expression.

关 键 词：马齿苋多糖 肝硬化 实验性 TGF-Β/SMAD信号通路 

分 类 号：R285.5[医药卫生—中药学]