重组人内抑素诱导佐剂性关节炎大鼠滑膜细胞凋亡的研究  

Experimental investigation on recombinant human endostatin induced apoptosis of synoviocytes in adjuvant arthritis rats

作　　者：夏丽娟[1] 陈飞虎[1] 阮晶晶[1] 刘永靖[1] 袁凤来[1] 宣尧仙[2] 

机构地区：[1]安徽医科大学药学院,安徽合肥230032 [2]浙江省医学科学院国家新药安全性评价研究重点实验室,浙江杭州310013

出　　处：《中国药理学通报》2008年第8期1027-1031,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30572196)

摘　　要：目的以弗氏完全佐剂诱导的佐剂性关节炎(AA)大鼠为动物模型,观察重组人内抑素诱导AA大鼠滑膜细胞凋亡的作用。方法分离、培养滑膜细胞,噻唑蓝(MTT)比色法检测重组人内抑素体内用药对滑膜细胞增殖的影响;用缺口末端标记法(TUNEL)及流式细胞仪检测重组人内抑素对AA滑膜细胞凋亡的影响。结果AA大鼠表现为滑膜细胞异常增殖,rh-End(1.25、2.5、5.0mg·kg-1)体内治疗给药及rh-End6.25～50mg·L-1浓度范围体外给药可抑制AA大鼠成纤维样滑膜细胞的增殖反应。rh-End体内用药可诱导AA大鼠滑膜组织及细胞的凋亡,rh-End体外用药作用48h,AnnexinV/PI双染色法观察到大鼠AAFLS凋亡率为1.77%,rh-End(25mg·L-1)可诱导AA大鼠FLS的凋亡,其凋亡率为6.67%。结论rh-End可不同程度抑制FLS的增殖反应,并诱导其凋亡的发生,减轻AA大鼠增生性滑膜炎。上述结果提示炎症增生的滑膜细胞可能是rh-End的另一个作用靶点。Aim To investigate the effect of recombi- nant human endostatin （rh-End） on apoptosis of synoviocytes in adjuvant arthritis （AA） rats. Methods Synoviocytes from rat knees were excised and cultured. The proliferation of synoviocytes was measured by MTT. The apoptosis of AA synoviocytes were determined by TUNEL and flow eytometry. Results rh- End（1.25,2.5,5.0 mg · kg-1· d-1,d 10-16） or different concentrations of rh-End （ 6. 25 - 50 mg · L-l） in vitro could decrease the proliferation of syno- vioeytes in AA rats. rh-End induced the apoptosis of synovium and synoviocytes in vivo. After stimulated by rh-End for 48h in vitro, Annexin V/PI diplo-staining founded that the apoptosis rate of AA FLS were 6. 67%, while AA FLS was 3.32%. Conclusions rh-End could decrease the hyperproliferation of FLS and induce apoptosis of it, the proliferative synovitis in AA rats were then lessened. The results suggested that the AA FLS might be another target of rh-End.

关 键 词：重组人内抑素 佐剂性关节炎 滑膜细胞 凋亡 

分 类 号：R-332[医药卫生] R322.72