强骨胶囊经p38-丝裂原活化的磷酸激酶信号通路对膝关节骨性关节炎的作用机制

A mechanistic study on the action of Qianggu Capsule on knee osteoarthritis via p38-mitogen-activated phosphokinase signaling pathway

目的探究强骨胶囊经p38-丝裂原活化的磷酸激酶(p38MAPK)信号通路对膝关节骨性关节炎(KOA)的作用机制。方法选取清洁级SD大鼠200只,采用随机数字表法分为对照组、模型组、低剂量组、中剂量组、高剂量组,每组40只。模型组、低剂量组、中剂量组、高剂量组建立左侧KOA大鼠模型,从造模第3 d开始,低剂量组、中剂量组、高剂量组分别给予强骨胶囊25 mg·kg^(-1)·d(-1)、108 mg·kg^(-1)·d(-1)、225 mg·kg^(-1)·d(-1)灌胃,对照组不造模,对照组及模型组给予等体积生理盐水灌胃。结果灌胃第2、4周,模型组MEK-3/6[(61.95±4.02)%、(43.26±3.54)%]、P-MEK-3/6[(56.92±3.62)%、(39.15±3.49)%]、p38[(67.92±3.51)%、(46.85±3.16)%]、P-p38[(56.43±3.14)%、(28.16±3.01)%]阳性百分比均高于对照组(P<0.05),低剂量组、中剂量组、高剂量组MEK-3/6、P-MEK-3/6、p38、P-p38阳性百分比均低于模型组(P<0.05);模型组灌胃第2、4周软骨细胞的凋亡率[(25.36±4.72)%、(21.69±4.29)%]均高于对照组,增殖OD值[(0.05±0.01)、(0.06±0.01)]均低于对照组(P<0.05);低剂量组、中剂量组、高剂量组第2、4周软骨细胞的凋亡率均低于模型组,增殖OD值均高于模型组(P<0.05)。结论强骨胶囊可有效抑制KOA大鼠p38MAPK信号通路,发挥抑制软骨细胞凋亡、促进软骨组织修复的作用。

Objective To investigate mechanism underlying the action of Qianggu Capsule on knee osteoarthritis(KOA)via the p38-mitogen-activated phosphokinase(p38MAPK)signaling pathway.Methods A total of 200 clean SD rats were selected and divided into the control group,model group,low-,medium-,and high-dose groups by random number table(n=40 each).Left KOA was modeled in rats of the model group,low-,medium-,and high-dose groups.Starting from day 3 after the modeling,the low-,medium-,and high-dose groups were given Qianggu Capsule by gavage at doses of 25,108,and 225 mg·kg^(-1)·d(-1),respectively.The control group was not modeled for KOA.Gavage of normal saline at equal volume was given to the control group and model group.Results In weeks 2 and 4 of the gavage,the model group showed higher rates of positivity for MEK-3/6[(61.95±4.02)%and(43.26±3.54)%],P-MEK-3/6[(56.92±3.62)%and(39.15±3.49)%],p38[(67.92±3.51)%and(46.85±3.16)%],and P-p38[(56.43±3.14)%and(28.16±3.01)%]compared with the control group(P<0.05).In any of the low-,medium-,and high-dose groups,the rates of positivity for MEK-3/6,P-MEK-3/6,p38,and P-p38 were lower than those in the model group(P<0.05).In weeks 2 and 4 of the gavage,the model group showed higher apoptosis rates of chondrocytes[(25.36±4.72)%and(21.69±4.29)%]and lowered proliferation as measured by OD values[(0.05±0.01)and(0.06±0.01)],compared with the control group(P<0.05).In any of the low-,medium-,and high-dose groups,the apoptosis rates of chondrocytes were lower,and the OD values were higher,than those in the model group in weeks 2 and 4(P<0.05).Conclusion In KOA rats,Qianggu Capsule can effectively inhibit the p38MAPK signaling pathway,inhibit chondrocyte apoptosis and promote cartilage repair.