从 P38丝裂原活化蛋白激酶信号通路探讨金天格胶囊防治膝骨关节炎临床研究

摘要

Objective By observing the change in P38-MAPK signal pathway and score of clinical manifestations, to investigate the mechanism of Jintiange capsules in the prevention and treatment of the knee osteoarthritis ( KOA) .Methods Seventy-eight patients with KOA, who conformed to the diagnosis criteria and including criteria, were selected and randomly divided into two groups:intervention group and control group.Patients in intervention group were treated with Jintiange capsules for 12 weeks, while patients in control group were treated with alendronate sodium for 12 weeks.The scores of KOA clinical manifestation were documented before and after the treatment.The changes of MKK4, P38α, P38γ, and MMP13 mRNA were detected using real-time PCR.Results The total effective rate in intervention group was 76.92%, while the total effective rate in control group was 58.97%.The difference between the two groups was significant ( P<0.05 ) .Before the treatment, the VAS score in two groups was 6.20 ±1.71 and 6.27 ±1.86, respectively.And there was no difference between the two groups (P >0.05).After the treatment, the VAS score in both groups declined.After 1-week treatment, no significant differenct of the VAS score between the two groups was observed (P>0.05).But after 4-week and 12-week treatment, the VAS score in intervention group was significant lower than that in control group ( P<0.05 ) .Before the treatment, the indexes of P38-MAPK signal pathway and the MMP-13 mRNA increased in KOA patients.After the treatment, the changes of P38γand MMP13 mRNA decreased significantly compared with that before the treatment (P<0.05).However, the expression of MKK4 and P38αshowed no significant difference compared with that before the treatment ( P >0.05 ) .Conclusion Jintiange capsules exert clear effect in the treatment of KOA by regulating P38-MAPK signal pathway and by reducing the expression of MMP-13.%目的：基于检测P38丝裂原活化蛋白激酶信号通路中相关指标及其临床症状积分，探讨金天格胶囊防治膝骨关节炎的临床疗效及其可能机制。方法符合诊断标准、纳入标准、排除标准78例膝关节炎患者，按就诊顺序，1∶1随机分为治疗组和对照组，治疗组予金天格胶囊、对照组予阿伦磷酸钠，连续干预12周，分别收集治疗前、治疗后1周、4周及12周症状积分变化；应用荧光定量PCR技术检测治疗前及治疗12周后关节液中P38α、P38γ、MMP－13变化。结果治疗组总有效率76．92％，对照组总有效率58．97％，经统计学比较，治疗组明显优于对照组（ P＜0．05）。治疗前，两组患者VAS计分分别为（6．20±1．71）、（6．27±1．86），经比较无统计学意义（ P＞0．05），具有可比性；治疗后，两组患者VAS评分均呈下降趋势，治疗后1周两组患者VAS积分比较无统计学意义；治疗后4周、12周治疗组VAS积分低于对照组，经统计学比较，有显著性差异（ P＜0．05）。治疗前，KOA患者P38－MAPK信号通路中相关指标及MMP－13 mRNA变化均呈上升趋势；治疗后，治疗组MKK4、P38αmRNA变化较治疗前比较，无明显差异（P＞0．05）；而P38γ、MMP13 mRNA变化呈下降趋势，较治疗前比较，有统计学差异（P＜0．05）。结论金天格胶囊具有明确缓解膝关节炎疼痛效用，其疗效机制可能与调节P38丝裂原活化蛋白激酶信号通路，较少MMP－13表达相关。