富血小板血浆对膝骨关节炎相关细胞因子的影响

Curative effect of platelet-rich plasma in treatment of knee osteoarthritis and influences on serum cytokines levels

目的探讨富血小板血浆治疗膝骨关节炎(OA)的临床疗效及其对血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-13(MMP-13)、肿瘤坏死因子-α(TNF-α)水平的影响。方法招募于2017年1月至5月单号选择漳州市解放军第909医院门诊就诊的膝关节OA患者符合Kellgren-Lawrence(K-L)分级(Ⅱ~Ⅲ级)分级标准设置为富血小板血浆(PRP)组40例,双号选择漳州市解放军第909医院门诊就诊的膝关节OA患者符合K-L分级(Ⅱ~Ⅲ级)分级标准设置为透明质酸钠(SH)组40例,招募后统计两组患者年龄平均(53±3)岁,其中男33例,女47例;左膝35例,右膝45例,分别采用PRP和SH关节腔内注射进行治疗。两组患者于治疗前及首次治疗后3、6、12个月,通过视觉模拟评分(VAS),西安大略麦马斯特大学骨关节炎指数可视化量表(WOMAC)及膝关节X线总评分以评估临床疗效,酶联免疫法检测血清IL-1β、IL-6、MMP-9、MMP-13、TNF-α含量的变化,两组间各时间点比较采用t检验,两组内各时间点比较采用重复测量方差分析。结果80例患者中,77例完成随访,PRP组39例,SH组38例。两组患者治疗前WOMAC分级评分、膝关节X线总评分,血清中细胞因子的表达水平无统计学意义(P>0.05)。与治疗前相比,PRP组治疗3、6个月后患者的VAS评分,WOMAC评分,膝关节X线总评分,血清IL-1β、IL-6、MMP-9、MMP-13、TNF-α含量均降低,差异均有统计学意义(t值分别为:1.14、4.673、0.410、9.852、7.845、12.03、6.108、11.66、11.34、13.89、9.779、15.83、13.71、28.84、7.182、27.76,均为P<0.05);与治疗前相比,SH组治疗后3、6、12个月治疗后膝关节X线总评分,血清IL-1β、IL-6、MMP-9、MMP13、TNF-α含量无明显改变,差异无统计学意义(P>0.05);6、12个月两组患者的VAS评分,WOMAC评分,膝关节X线总评分,血清IL-1β、IL-6、MMP-9、MMP-13、TNF-α含量对比,PRP组表现明显优于SH组,差异具有统计学意义(t值为分别为:-5.316、-10.943、-9.804、-9.554、-11.829、-14.256、-11.664、-10.259、-13.732、-12.837、-15.708、-12.919、-28.607、-20.693、-27.623、-23.344,均为P<0.05)。结论膝关节腔内注射自体PRP与SH,近期效果类似,治疗6、12个月后临床效果优于透明质酸钠,能有效改善患者的疼痛,控制病情的迁延,降低分解性细胞因子表达水平,值得临床推广应用。

Objective To observe the curative effect of platelet rich plasma(PRP)intra-articular injection in the treatment of knee osteoart-hritis and the effect of serum interleukin(IL)-1β、IL-6,matrix metalloprotein(MMP)-9,MMP-13,tumor necrosis factor-α(TNF-α)level.Methods A total of 80 patients with knee osteoarthritis of gradeⅡandⅢ(Kellgren-Lawrence classification)were assigned to the platelet-rich plasma(PRP)and sodium hyaluronate(SH)group according to the date of consultation,38 cases in SH group and 39 cases in PRP group had got the complete follow-up.Both the two groups adopted intra-articular injection.All the patients were prospectively evaluated before the treatment and at the third,sixth and 12th month after the treatment by the visual analogue scale(VAS)scores,the Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and the X-ray score of the knee.The changes of serum IL-1β、IL-6、MMP-9、MMP-13、TNF-αwere observed by enzyme-linked immunosorbent assay(ELISA).Between the two groups serum cytokines levels were compared using t test at each time point,within the groups the levels were compared by repeated measures analysis of variance.Results Among the 80 patients,77 were followed up,39 in PRP group,38 in SH group.At the three,six and 12 months after the treatment,the levels of the cytokines,VAS,WOMAC and the X-ray scores of the PRP group were lower than before.There were significant differences between the two groups(t=1.14,4.673,0.410,9.852,7.845,12.03,6.108,11.66,11.34,13.89,9.779,15.83,13.71,28.84,7.182,27.76,all P<0.05).At the three,six and 12 months after the treatment,there was no significant change ofcytokinesand the X-ray score of the SH groups(t=-5.316,-10.943,-9.804,-9.554,-11.829,-14.256,-11.664,-10.259,-13.732,-12.837,-15.708,-12.919,-28.607,-20.693,-27.623,-23.344,all P>0.05).No serious adverse event was detected in the two groups.According to the follow-up evaluations,both the groups presented clinical improvements at three months after the treatment.(P<0.05).The improvement of all above indexes in PRP group were more significant than those in SH group at the six and 12 months after the treatment(P<0.05).Conclusion PRP intra-articular injection has similar short-term effect compared with SH,while after six or 12 months of treatment,the clinical effect of PRP with superior pain relief is better than SH.