目的：探讨肿瘤坏死因子样弱凋亡诱导因子（tumor necrosis factor-like weak inducer of apoptosis ，TWEAK）对体外培养的大鼠关节软骨细胞产生趋化因子的影响，初步了解 TWEAK 在OA发病机制中的作用。方法：体外培养大鼠关节软骨细胞，实验组细胞用250 ng/mL TWEAK诱导，对照组则不作此处理，24、48、72 h后检测两组细胞培养液中趋化因子白细胞介素-8（interleukin-8，IL-8）、单核细胞趋化蛋白-1（monocyte chemotactic protein 1，MCP-1）、受激活调节正常T细胞表达和分泌因子（regulated upon activation normal T cell expressed and secreted factor ，RANTES）和巨噬细胞炎性蛋白-2（macrophage in-flammatory protein 2，MIP-2）的含量。结果：TWEAK诱导24、48、72 h后，实验组大鼠关节软骨细胞上清液中RANTES含量均明显高于相应对照组（P＜0．05），且RANTES的含量与TWEAK作用时间呈正相关（P＜0．05）；实验组IL-8和MCP-1的含量在TWEAK诱导48、72 h后均明显高于相应对照组（P＜0．05），但与TWEAK作用时间无相关性（P＞0．05）；MIP-2的浓度在TWEAK诱导48、72 h后均明显低于相应对照组（均 P＜0．05），且其含量的降低与 TWEAK 作用时间呈正相关（P＜0．05）。结论：TWEAK能诱导体外培养的大鼠关节软骨细胞产生趋化因子（IL-8、MCP-1、RANTES），以此参与OA的发生。%Objective:To explore the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on generating chemokines in rat articular chondrocytes cultured in vitro ,and to understand its role in the pathogenesis of OA .Methods :Rat articular chondrocytes were cultured in vitro .The cells of experimental group were induced by 250 ng/mL TWEAK ,while the cells of the control group were not .Levels of chemokines interleukin-8(IL-8) ,monocyte chemotactic protein 1(MCP-1) ,regu-lated upon activation normal T cell expressed and secreted factor (RANTES) ,macrophage inflammatory protein 2(MIP-2) in the nutrient solution of the two groups were detected at 24 ,48 and 72 h .Results:After the induction of TWEAK ,the levels of RANTES in the supernatant of rat articular chondrocytes at 24 ,48 and 72 h were all significantly higher than those in the con-trol groups ,respectively (all P<0 .05) ,and the contents of RANTES were positively correlated with the treatment time of TWEAK (P<0 .05) .The IL-8 and MCP-1 levels in the supernatant of rat articular chondrocytes at 48 and 72 h were signifi-cantly higher than those in the control groups (both P< 0 .05) ,but they had no correlations with the treatment time of TWEAK (P>0 .05) .The MIP-2 levels of the rat articular chondrocytes supernatant at 48 and 72 h were significantly lower than those in the control groups (P<0 .05) ,and the contents of MIP2 were positively correlated with the treatment time of TWEAK (P<0 .05) .Conclusions :TWEAK can induce rat chondrocytes in vitro to generate chemokines (IL-8 ,MCP-1 ,RAN-T ES ) ,so that it is involved in the occurance of OA .
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