复方莪术散加减联合西药对Ⅲ~Ⅳ期子宫内膜异位症术后复发的影响及作用机制研究

Study on Influence of Modified Fufang Ezhu Powder Combined with Western Medicine on Postoperative Recurrence of Patients with Stage Ⅲ-Ⅳ Endometriosis and Mechanism

目的 探讨复方莪术散加减联合西药对Ⅲ~Ⅳ期子宫内膜异位症(Endometriosis,EM)术后复发的影响及作用机制。方法 选取2019年1月—2021年10月期间在苏州市中西医结合医院接受手术治疗的Ⅲ~Ⅳ期EM患者120例,按随机数字表法分为对照组与观察组,每组各60例。所有患者均接受腹腔镜下EM病灶切除术,对照组术后使用醋酸亮丙瑞林缓释微球(GnRH-a)联合反向添加疗法,观察组在对照组基础上口服复方莪术散加减治疗,两组患者均治疗3个月。观察比较两组患者临床疗效、复发及不良反应发生情况,治疗前后中医证候评分和EM的专用生存质量评价量表(Endometriosis Patient Quality of Life Scale-5,EHP-5)评分,检测血清性激素[雌二醇(Estradiol,E_(2))、黄体生成素(Luteinizing hormone,LH)、卵泡刺激素(Follicle stimulating hormone,FSH)和孕酮(Progesterone,P)]、血清癌抗原125(Cancer antigen 125,CA125)、人附睾分泌蛋白4(Human epididymal secreted protein 4,HE4)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)、基质金属蛋白酶-2(Matrix metalloproteinase-2,MMP-2)、基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和白介素-6(Interleukin-6,IL-6)水平。结果 治疗后观察组总有效率98.33%(59/60)明显高于对照组86.67%(52/60),差异有统计学意义(P<0.05)。治疗后两组患者中医证候评分和EHP-5评分较治疗前明显降低,且观察组的评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清FSH、LH、E_(2)、P水平较治疗前明显降低,且观察组较对照组降低更明显,差异有统计学意义(P<0.05)。治疗后两组患者血清CA125、HE4、VEGF、MMP-2、MMP-9、TNF-α和IL-6水平较治疗前降低,且观察组均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。随访6个月,观察组复发1例(1.67%),对照组复发8例(13.33%),观察组复发率明显低于对照组,差异有统计学意义(P<0.05)。结论 Ⅲ~Ⅳ期EM患者术后应用复方莪术散加减联合西药可明显缓解临床症状及体征,提高临床疗效并降低复发率,改善血性激素紊乱,其机制可能与调节CA199、HE4、MMP-2、MMP-9、TNF-α和IL-6等有关。

Objective To investigate the influence of modified Fufang Ezhu Powder combined with western medicine on postoperative recurrence of patients with stage Ⅲ-Ⅳ endometriosis(EM)and mechanism.Methods From January 2019 to October 2021,120 patients with stage Ⅲ-Ⅳ EM who received surgical treatment in Suzhou Integrated Traditional Chinese and Western Medicine Hospital were selected and divided into a control group and observation group according to a random number table,with 60 patients in each group.All patients underwent laparoscopic resection of the EM lesion.The control group was treated with leuprorelin acetate sustained-release microspheres(GnRH-a)combined with addback therapy for three months after surgery,and the observation group was treated with modified Fufang Ezhu Powder for three months.The clinical efficacy,recurrence,and adverse reactions of the two groups were compared,and the traditional Chinese medical syndrome score and EM patient quality of life scale-5(EHP-5)before and after the treatment were evaluated.The serum sex hormone indicators including luteinizing hormone(LH),follicle-stimulating hormone(FSH),estradiol(E_2),and progesterone(P),were detected.Cancer antigen 125(CA125),human epididymal secreted protein 4(HE4),vascular endothelial growth factor(VEGF),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were also detected.Results After treatment,the total effective rate of the observation group was 98.33%(59/60),higher than 86.67%(52/60)of the control group(P<0.05).After treatment,the traditional Chinese medical syndrome scores and EHP-5 scores of the two groups of patients were significantly reduced,and the scores of the observation group were lower than those of the control group,so the differences were statistically significant(P<0.05).After treatment,the serum levels of LH,FSH,E_2,and P were significantly reduced in the two groups,and the observation group was lower than the control group(P<0.05).After treatment,the serum levels of CA125,HE4,MMP-2,MMP-9,TNF-α,and IL-6 were significantly reduced in the two groups,and the observation group was lower than the control group(P>0.05).During the treatment,there was no significant difference in the incidence of adverse reactions between the two groups(P<0.05).During the 6-month follow-up period,there was one case(1.67%)of recurrence in the observation group and eight cases(13.33%)of recurrence in the control group,and the recurrence rate in the observation group was significantly lower than that in the control group(P<0.05).Conclusion The postoperative application of modified Fufang Ezhu Powder combined with western medicine can significantly alleviate the clinical symptoms and signs of patients with stage Ⅲ-Ⅳcombined with western medicine can significantly alleviate the,and improve the blood hormone disorder.The mechanism may be related to the regulation of CA199,HE4,MMP-2,MMP-9,TNF-α,IL-6,etc.