芪术颗粒对肝纤维化模型大鼠肝窦微血管新生的影响及其机制研究  

Effect of Qi Zhu Granule on Microvascular Regeneration in Sinusoidal Endothelial Cells of Rats with Hepatic Fibrosis and Its Mechanism

作　　者：张荣 刘绍能[1] 周海艳[1] 马继征[1] 丁佳媛 刘慧敏[1] 张玲[1] 路迎冬[1] ZHANG Rong;LIU Shaoneng;ZHOU Haiyan;MA Jizheng;DING Jiavuan;LIU Huimin;ZHANG Ling;LU Yingdong(Guang' anmen Hospital of Chinese Academy of Traditional Chinese Medicine,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院消化内科

出　　处：《中药新药与临床药理》2019年第6期659-663,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81573917)

摘　　要：目的观察芪术颗粒对四氯化碳(CCl4)诱导的肝纤维化大鼠模型肝窦微血管新生的影响及其机制研究。方法将24只Wistar大鼠随机分为正常对照组、模型对照组、复方鳖甲软肝片组和芪术颗粒组,除正常对照组外其余各组腹腔注射CCl4建立大鼠肝纤维化模型。分别干预治疗4周后处死大鼠,取肝脏组织,免疫组化方法染色,检测血小板内皮细胞粘附分子(CD31)、高度糖基化的i型跨膜糖蛋白(CD34)的表达,并进行图像分析;另以CD31、CD34为对象进行微血管密度分析;Western Blot法检测毛细血管内皮表达Ⅷ因子相关抗原(vWF)、陷窝蛋白(Caveolin-1)的蛋白表达。结果与正常对照组比较,模型对照组的新生微血管密度(MVD)明显增多,肝窦内皮细胞(LSEC)中CD31、CD34、vWF、Caveolin-1表达增强(P<0.01);与模型对照组比较,芪术颗粒组中的MVD值及LSEC中CD31、CD34、vWF、Caveolin-1蛋白表达量均显著降低(P<0.01,P<0.05)。结论芪术颗粒可降低肝纤维化中肝窦微血管密度,减少肝窦微血管增生,防止肝窦毛细血管化,其机制可能与其下调LSEC中CD31、CD34、vWF、Caveolin-1表达有关。Objective To observe the effect and mechanism of Qi Zhu granule on hepatic sinus microangiogenesis induced by carbon tetrachloride(CC14)in rat models of hepatic fibrosis.Methods Twenty-four Wistar rats were randomly divided into normal control group,model control group,Fufang Biejia Ruangan ttiblets group and Qi Zhu granule group.Except the normal control group,the rats in the rest of groups were intraperitoneally injected with CCL to establish rat liver fibrosis models.The rats were intervened for 4 weeks,and the liver tissues were taken.Immuno histochemical staining and image analysis were used to detect expression of platelet endothelial cell adhesion molecules CD31 and highly glycosylated i-type transmembrane glycoprotein(CD34);for microvascular density(MVD)of CD31,CD34 was also analyzed;Western Blot analysis was used to detect capillary endothelial expression of factor VIII-related antigen(vWF),and Caveolin-1.Results Compared with the model control group,the MVD in new blood vessels of the Qi Zhu granule group rats was decreased(P<0.05).The expression levels of CD31,CD34,vWF and Caveolin-1 in the liver sinusoidal endothelial cells(LSEC)of model group rats were higher,that were all significantly lower in the granule group rats(P<0.05).Conclusion Qi Zhu granule Ccin reduce the growth of hepatic sinusoidal microvessels and prevent vascular regenenition in hepatic fibrosis,and the mechanism may be related to the down-regulation expression of CD31,CD34,vWF,Caveolin-1 in LSEC.

关 键 词：芪术颗粒 血管新生 Ⅷ因子相关抗原 陷窝蛋白-1 肝窦 

分 类 号：R285.5[医药卫生—中药学]