虫草菌丝提取物对DMN诱导肝纤维化大鼠肝窦内皮细胞通透性影响  

Effect of Cordyceps mycelia extract on hepatic sinusoidal endothelial cells permeability in dimethylnitrosamine-induced liver fibrosis in rats

作　　者：唐志鹏[1] 刘平[2] 王宪波[2] 

机构地区：[1]上海中医药大学附属龙华医院消化内科,上海200032 [2]上海中医药大学肝病研究所,上海201203

出　　处：《中国新药与临床杂志》2006年第9期713-717,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家杰出青年基金(39825128);上海市重点学科项目资助

摘　　要：目的：研究二甲基亚硝胺(DMN)诱导大鼠肝纤维化模型肝窦内皮细胞(SECs)通透性变化模式,以及虫草菌丝提取物(CME)对SECs通透性的影响,以阐明其抗肝纤维化的作用机制。方法：采用DMN 10μg·kg^(-1)腹腔注射,每周3次,连续4wk的方法制作大鼠肝纤维化模型。按10mg·kg^(-1)·d^(-1)剂量给予CME干预和治疗模型大鼠,qd,连续2wk和4wk。透射电镜观察肝组织超微结构。免疫组织化学染色法观察肝窦壁CD31和小窝蛋白1(Car-1)表达。结果：正常肝窦壁SECs有许多窗孔,CD31和Cav-1呈现弱阳性染色。给予DMN刺激后,模型组大鼠肝窦壁SECs窗孔数量逐渐减少,CD31和Cav-1阳性染色细胞逐渐增多,至4wk末时到达峰值；停止DMN刺激后,模型对照组大鼠肝窦壁SECs窗孔数量逐渐增多,CD31和Car-1阳性染色细胞逐渐减少。经2wk和4wk处理后,与模型组和模型对照组比较,CME预防组和治疗组大鼠肝窦壁SECs窗孔数量显著增多,CD31和Cav-1阳性染色细胞逐渐显著减少。结论：在DMN诱导大鼠肝纤维化形成过程中,SECs表型发生变化,其通透性模式由以窗孔运送为主转变为以小窝运送为主,使通透性减少。CME能够改善SECs通透性,这可能是其抗肝纤维化作用机制之一。AIM： To study the mode of hepatic sinusoidal endothelial cells （SECs） permeability in dimethylnitrosamine （DMN） -induced liver fibrosis in rats and the effect of Cordyceps mycelia extract （CME） on SECs permeability in order to explore the anti-fibrosis mechanism of CME. METHODS： The liver fibrosis model was established by peritoneal injection of DMN （at a dose of 10 mg.kg^-1, 3 times.wk^-1, for 4 wk） in rats. The rats of the CME-prevented group and CME-treated group were administrated with CME at a dose of 10 mL. kg^-1.d^-1, qd, for 2 and 4 wk. Ultrastructure of liver tissue was observed under transmission electron microscope （TEM）. CD31 and cavedin-1 （Cav-1） expressions of sinusoid walls were assessed with immunohistochemical technique. RESULTS： There were many fenestrae, a little CD31 and Cav-1 positive staining in normal liver sinusoidal walls. When exposed to DMN, the number of fenestrae gradually decreased and the number of CD31 and Cav-1 positive staining gradually increased. The strongest positive staining of them displayed in the 4 wk model rats. When DMN was withdrawn, the number of fenestrae gradually increased and the number of CD31 and Cav-1 positive staining gradually decreased in the model control rats. After 2 and 4 wk treatment, the number of fenestrae significantly increased, and the number of CD31 and Cav-1 positive staining significantly decreased in the CME-prevented and CME-treated group compared to model and model control group respectively （CME-prevented vs model group： CD31 positive area （%） ： 1.53 ± 0.41 vs 3.94 ± 0.70 （2 wk）, 2.51 ＋ 0.77 vs 6.09± 1.16 （4wk）; Cav-1 positive area （%）： 2.05 ± 0.63vs 3.98 ± 0.94 （2wk）, 2.27 ± 0.78vs 7.69± 1.71 （4 wk） . CME-treated vs model control group： CD31 positive area （%）： 2.01± 0.67 vs 4.35 ± 1.02 （2 wk）, 1.16 ±± 0.28 vs 3.01± 0.52 （4 wk） ： Cav-1 positive area （%） ： 2.01 ±0.67 vs 5.62 ± 1.39 （2 wk）, 1.61 ± 0.35 vs 3.01 ± 0.94 （4 wk）, P 〈 0.

关 键 词：肝硬化 实验性 细胞膜通透性 大鼠 二甲基亚硝胺 肝窦内皮细胞 窗孔 小窝蛋白1 虫草菌丝提取物 

分 类 号：R36[医药卫生—病理学] R282.7[医药卫生—基础医学]