p-moesin在血吸虫病肝纤维化鼠肝窦内皮细胞中的表达及意义

目的:动态观察血吸虫病肝纤维化鼠肝窦内皮细胞moesin表达水平的时相变化,探讨其与肝窦内皮细胞失窗孔化的关系。方法:采用腹部敷贴法感染血吸虫尾蚴建立血吸虫病性小鼠肝纤维化模型,除正常对照组(A组,10只)外,78只成模小鼠分为血吸虫病组(B组,24只)、吡喹酮(Biltricide)杀虫片治疗组(C组,18只)、Rock抑制剂(Hydroxyfasudil)治疗组(D组,18只)、Biltricide+Hydroxyfasudil治疗组(E组,18只),分别于治疗第16周、19周、21周分批剖腹取各组小鼠肝组织进行HE、Masson染色;同时Western blotting检测p-moesin蛋白表达,透射电镜观察超微结构。结果:与A组相比,B组肝组织p-moesin蛋白表达量增加。给予药物干预后,D组、E组p-moesin蛋白降低,16周时最为明显,但D组于19周开始逐渐恢复到原水平,而E组继续下降,明显低于D组。肝窦超微结构观察,药物干预21周时,C组与D组相比,肝组织炎性细胞明显减少,Disse腔内胶原纤维有所减少,但肝窦内皮细胞窗孔、肝窦内皮下基底膜无明显好转。E组与C组比较肝细胞器形态明显恢复,可见窗孔,未见基底膜。结论:血吸虫病肝纤维化小鼠肝窦内皮细胞通过p-moesin蛋白表达上调,参与肝窦内皮细胞失窗孔化,从而引起肝内微循环障碍。

Expression of p-moesin in Sinusoidal Endothelial Cell of Schistosomal Hepatic Fibrosis Mice

Objective: To observe the expression of moesin in sinusoidal endothelial cell of schistosomal hepatic fibrosis mice, and to explore the possible association of moesin with hepatic sinusoidal endothelial fenestrae. Method: The liver fibrosis model was established by abdominal infected with schistosomal cercaria in 88 mice,treated with biltricide in 13W and hydroxyfasudil in 14W.And then they were divided into the following 5 groups:control group(A group,n=10),model group(B group,n=24),treated with biltricide group(C group,n=18),treated with hydroxyfasudil group(D group,n=18),treated with biltricide+hydroxyfasudil group(E group,n=18).In 13W(A group 10 mice and B group 6 mice),in 16W,19W and 21W(B,D,C,E group,each group 6 mice),the mice were sacrificed,respectively.The relative area of liver fibrosis on pathological section was semi-quantitatively determined and assessed by HE,Masson stain,electonmicrocopy and immunohistochemistry.And p-moesin protein expressions were assessed by Western blot. Results: Compared with A group, the protein expression of p-moesin was increased(P<0.05)in B group.After intervension with biltricide and/or hydroxyfasudil, the expression of p-moesin in E group was markedly lower than that of D group(P<0.05).Electonmicrocopy show liver sinusoidal of the mice in E group was significantly recovered compared with other groups.And there was no difference between B group and D group. Conclusion: Our results suggest that an upregulation of p-moesin that contributes to disappearance of hepatic sinusoidal endothelial fenestrae may involve sinusoidal capillarization with schistosomal hepatic fibrosis mice.