莪术醇干预肝纤维化病程中的肝窦毛细血管化病变的研究  

Effects of Curcumol on Proliferation of Sinusoidal Endothelial Cells and Sinusoidal Capillarization in Liver Fibrosis

作　　者：彭岳 杨妙 林江 赵铁建 刘鹏 刘茜玉 郭伟倩 PENG Yue;YANG Miao;LIN Jiang;ZHAO Tiejian;LIU Peng;LIU Qianyu;GUO Weiqian(School of Basic Medicine,Guangxi University of Traditional Chinese Medicine,Nanning 530000,Guangxi,China;Graduate School,Guangxi University of Traditional Chinese Medicine,Nanning 530000,Guangxi,China)

机构地区：[1]广西中医药大学基础医学院,广西南宁530000 [2]广西中医药大学研究生学院,广西南宁530000

出　　处：《辽宁中医杂志》2024年第12期9-14,I0017,共7页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81960761,82060825,81960751);广西自然科学基金项目(2020GXNSFAA297119);中医学广西一流学科(桂教科研〔2022〕1号);广西名中医林江传承工作室(桂中医药科教发〔2021〕6号);广西研究生教育创新计划项目(YCSZ2022002);广西高发传染病中西医结合转化医学重点实验室。

摘　　要：目的从肝窦内皮细胞的活率、窗孔大小、基底膜面积、肝星状细胞的增殖率及凋亡率等情况入手,研究莪术醇对肝窦毛细血管化病变的干预及其机制。方法将莪术醇分别与肝窦内皮细胞和肝星状细胞孵育。以MTT比色法分别测定两种细胞的活率及细胞增殖抑制率;以流式细胞术测定肝星状细胞的周期及细胞凋亡情况;以透射电镜观察肝窦内皮细胞的窗孔及基底膜等微结构的变化情况。结果莪术醇干预后,可使肝窦内皮细胞的窗孔增多及扩大;使细胞外形成了的基底膜变薄甚至消失;可降低活化了的肝星状细胞的增殖活力,并能诱导其发生细胞凋亡(均P<0.05)。且发现上述作用均具有剂量依赖性(P<0.05)。并且中、高浓度莪术醇的上述作用强度均高于治疗剂量的秋水仙碱和丹参酚酸B(P<0.05)。结论莪术醇可保护肝窦内皮细胞的活力;具有显著的抗“肝窦毛细血管化”的药理学作用。这是该药活血化瘀、抗肝纤维化作用的重要机制。Objective To investigate the intervention and mechanism of curcumin on hepatic sinusoid capillary metaplasia starting from the viability,pore size,basement membrane area,proliferation rate and apoptosis rate of hepatic stellate cells in the hepatic sinusoids.Methods Curcumol was incubated with hepatic sinusoidal endothelial cells and hepatic stellate cells.The cell viability and proliferation inhibition rate of hepatic sinusoidal endothelial cells and hepatic stellate cells were measured by MTT colorimetry.The cell cycle and apoptosis of hepatic stellate cells were measured by AnnexinV-FITC/PI double staining(flow cytometry).The microstructural changes of fenestrae and basement membrane of hepatic sinusoidal endothelial cells were observed by transmission electron microscopy.Results(1)After the intervention of leptin,the cell activity of hepatic sinusoidal endothelial cells decreased.The hepatic sinusoidal capillary was observed,including increased activity of hepatic stellate cells,decreased number and diameter fenestrae of hepatic sinusoidal endothelial cells,and continuous extracellular basement membrane.(2)After the intervention of leptin,curcumol can increase or enlarge the fenestrae of the hepatic sinusoidal endothelial cells,and make the basement membrane of hepatic sinusoidal endothelial cells thin or even disappear.It could decrease the activity of activated hepatic stellate cells and induce apoptosis,and the above results had significant difference(P<0.05).And with the concentration of curcumol increased,the above effects increased in a gradient,and the above effects were dose-dependent(P<0.05).In addition,the experimental results showed that the above-mentioned effects of curcumol in medium and high concentrations were significantly stronger than those of colchicine and salvianolic acid B at therapeutic doses(P<0.05).Conclusion Curcumol can protect the viability of hepatic sinusoidal endothelial cells,and has significant pharmacological effects against hepatic sinusoidal capillary.It can inhibit hepati

关 键 词：莪术醇 抗肝纤维化 肝窦毛细血管化 窗孔 基底膜 

分 类 号：R285[医药卫生—中药学]