依托咪酯调节MAPK/ERK信号通路对骨关节炎大鼠软骨损伤的影响  

Effect of Etomidate Modulation of MAPK/ERK Signaling Pathwayon Cartilage Damage in Osteoarthritic Rats

作　　者：甘志强[1] 张丹[1] 陈印 廖飞 GAN Zhiqiang;ZHANG Dan;CHEN Yin(Dazhou Hospital of Integrated Traditional Chinese and Western Medicine,Sichuan Dazhou 635000,China)

机构地区：[1]四川省达州市中西医结合医院麻醉科,四川达州635000

出　　处：《河北医学》2023年第2期208-214,共7页Hebei Medicine

基　　金：2019年第二批四川省卫生健康科研课题普及项目,(编号:19PJ305)。

摘　　要：目的:探究依托咪酯(ET)对骨关节炎(OA)大鼠软骨损伤的影响以及对丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)信号通路的调节作用。方法:将SPF级SD雄性大鼠72只,随机分6组:假手术组、模型组、阳性组(15mg/kg的双氯芬酸钠)以及ET低(1.5mg/kg)、中(3mg/kg)、高剂量(6mg/kg)组。评估各组大鼠关节水肿和承重不对称情况;检测各组大鼠压痛阈值和热痛阈值;HE观察各组大鼠软骨病理损伤情况并进行Mankin评分;酶联免疫吸附法(ELISA)测定大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)以及软骨寡聚基质蛋白(COMP)的水平;Western blot检验软骨组织中基质蛋白酶-13(MMP-13)及通路蛋白ERK及其磷酸化p-ERK蛋白的表达。结果:与假手术组相比,模型组大鼠右后肢膝关节水肿和关节承重不对称性增大,软骨组织缺损且软骨层变薄,软骨细胞数量变少,血清中TNF-α、IL-1β、COMP水平升高,软骨MMP-13、p-ERK1/2蛋白表达及p-ERK1/2/ERK1/2比例升高(P<0.05)。与模型组相比,阳性组和ET不同剂量组右后肢膝关节水肿和关节承重不对称性减小,软骨损伤被逐渐修复,细胞数量增多且排列均匀,软骨层变厚,血清中TNF-α、IL-1β、COMP水平降低,软骨MMP-13、p-ERK1/2蛋白表达及p-ERK1/2/ERK1/2比例降低(P<0.05)。结论:ET能够减轻OA大鼠软骨组织的病理损伤,降低血清中促炎因子的表达,可能通过抑制MAPK/ERK信号通路的活化实现。Objective:To investigate the effect of etomidate(ET)on cartilage damage in osteoarthritis(OA)rats and its regulation of mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:A total of 72 SPF SD male rats were randomly separated into 6 groups:sham operation group,model group,positive group(15mg/kg diclofenac sodium),and ET low(1.5mg/kg),medium(3mg/kg)and high-dose(6mg/kg)groups.The joint edema and weight-bearing asymmetry of the rats in each group were evaluated;the tenderness and thermal pain thresholds of rats in each group were detected;the pathological damage of cartilage in each group was observed by HE and Mankin score;the levels of tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β)and cartilage oligomeric matrix protein(COMP)in rat serum were determined by enzyme-linked immunosorbent assay(ELISA);and the expression of matrix protease-13(MMP-13)and pathway protein ERK and its phosphorylated p-ERK protein in cartilage tissue were determined by Western blot.Results:Compared with the sham-operation group,the right hind limb knee joint of the model group had edema and increased joint load-bearing asymmetry,cartilage tissue defects,and cartilage layer thinning,and the number of cartilage cells decreased,the levels of serum TNF-α,IL-1β,and COMP increased,the protein expression of MMP-13 and p-ERK1/2,and the ratio of p-ERK1/2/ERK1/2 in cartilage increased(P<0.05).Compared with the model group,the knee joint edema and joint load-bearing asymmetry of the right hind limb in the positive group and the different dose ET groups decreased,the cartilage damage was gradually repaired,the number of cells increased,the cells were evenly arranged,and the cartilage layer became thicker,the levels of serum TNF-α,IL-1β,and COMP decreased,the protein expression of MMP-13 and p-ERK1/2,and the ratio of p-ERK1/2/ERK1/2 in cartilage decreased(P<0.05).Conclusion:ET can alleviate the pathological damage of cartilage tissue in OA rats and reduce the expression of pro-inflamma

关 键 词：依托咪酯 MAPK/ERK 骨关节炎 软骨损伤 双氯芬酸钠 

分 类 号：R965[医药卫生—药理学]