鸢尾素靶向TDP-43调节p38MAPK通路对缓解骨关节炎的实验研究  

Experimental study on irisin targets TDP-43 to regulate p38MAPK pathway to relieve osteoarthritis

作　　者：张凤 史晓娟 祝子范 冯琳琳 张永峰 ZHANG Feng;SHI Xiao-juan;ZHU Zi-Fan;FENG Lin-lin;ZHANG Yong-feng(Department of Orthopedics,Xijing Hospital,Air Force Military Medical University,Xi’an 710032,Shaanxi,China)

机构地区：[1]空军军医大学西京医院骨科,陕西西安710032

出　　处：《解剖学研究》2021年第6期584-588,共5页Anatomy Research

摘　　要：目的探究鸢尾素靶向反式激活DNA结合蛋白43(Transactive response DNA binding protein 43,TDP-43)调节p38MAPK信号通路对骨关节炎(Osteoarthritis,OA)大鼠软骨细胞的干预机制。方法60只大鼠随机均分为Sham组、OA组、OA+鸢尾素组和OA+鸢尾素+SB203580组(n=15)。左侧膝关节腔内注射碘乙酸钠(30μl,10 d)构建OA模型,局部注射鸢尾素(0.5 mg/mL)和p38MAPK抑制剂SB203580(1 mg/kg)。比较各组大鼠膝关节水肿和承重情况,通过番红O染色检测软骨损伤。检测各组白细胞介素(IL)-1β和IL-6水平以及软骨组织中TDP-43 mRNA、蛋白以及p38蛋白磷酸化水平。结果4组大鼠各指标比较差异有统计学意义(P<0.05)。OA组的膝盖水肿、膝关节承重不对称性、IL-1β、IL-6、p-p38/p38显著高于Sham组(P<0.05),TDP-43mRNA和蛋白显著低于Sham组(P<0.05)。OA+鸢尾素组的膝盖水肿、膝关节承重不对称性、IL-1β、IL-6、p-p38/p38显著低于OA组(P<0.05),TDP-43 mRNA和蛋白显著高于OA组(P<0.05)。OA+鸢尾素+SB203580组的膝盖水肿、膝关节承重不对称性、IL-1β、IL-6、p-p38/p38显著低于OA+鸢尾素组(P<0.05)。OA+鸢尾素+SB203580组的TDP-43 m RNA和蛋白与OA+鸢尾素组比较差异无统计学意义(P>0.05)。结论鸢尾素可以通过调控TDP-43/p38MAPK抑制炎性反应,从而缓解软骨损伤。Objective To explore the mechanism of irisin-targeted transactive response DNA binding protein43(TDP-43)regulating p38 MAPK signaling pathway on chondrocytes in osteoarthritis(OA)rats.Methods 60 rats were randomly divided into Sham group,OA group,OA+irisin group and OA+irisin+SB203580 group(n=15).Sodium iodoacetate(30μl,10 days)was injected into the left knee joint cavity to construct an OA model.Irisin(0.5 mg/mL)and p38 MAPK inhibitor SB203580(1 mg/kg)were injected locally.The knee edema and weight bearing of rats in each group were compared.Safranin O staining was used to detect cartilage damage.The levels of interleukin(IL)-1βand IL-6 in each group and the phosphorylation levels of TDP-43 mRNA,protein and p38 protein in cartilage tissue were detected.Results The indicators of the four groups of rats were significantly different(P<0.05).Knee edema,knee joint weight bearing asymmetry,IL-1β,IL-6,and p-p38/p38 in OA group were significantly higher than those in Sham group(P<0.05),and TDP-43 mRNA and protein were significantly lower than those in Sham group(P<0.05).Knee edema,knee joint weight bearing asymmetry,IL-1β,IL-6,and p-p38/p38 in the OA+irisin group were significantly lower than those in the OA group(P<0.05),TDP-43 mRNA and protein were significantly higher than those in the OA group(P<0.05).Knee edema,knee joint weight bearing asymmetry,IL-1β,IL-6,and p-p38/p38 in the OA+irisin+SB203580 group were significantly lower than those in the OA+irisin group(P<0.05).There was no significant difference in TDP-43 mRNA and protein between the OA+irisin+SB203580 group and the OA+irisin group(P>0.05).Conclusion Irisin can inhibit inflammatory response by regulating TDP-43/p38 MAPK,thereby alleviating cartilage damage.

关 键 词：鸢尾素 骨关节炎 软骨 反式激活DNA结合蛋白43 促分裂素原活化蛋白激酶 

分 类 号：R684.3[医药卫生—骨科学]