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

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。

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

Aim To investigate the effect of recombinant 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 cytometry.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-1)in vitro could decrease the proliferation of synoviocytes 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.