基于代谢组学运用加减芎归补中汤治疗气虚血瘀型宫腔粘连分离术后临床研究

Clinical Study on Modified Xionggui Buzhong Decoction for Intrauterine Adhesions of Qi Deficiency and Blood Stasis Type After Transcervical Resection of Adhesions Based on Metabolomics

摘要:

目的：基于代谢组学观察加减芎归补中汤治疗气虚血瘀型宫腔镜下宫腔粘连分离术（TCRA） 术后的临床疗效。方法：将2023年4月—2024年12月在义乌市妇幼保健院就诊的气虚血瘀型宫腔粘连（IUA） 且行TCRA治疗的患者80例，按随机数字表法分为对照组与观察组各40例。对照组予芬吗通及阿司匹林联合治疗，观察组在对照组的基础上联合加减芎归补中汤治疗。2组均连续治疗3个月。比较2组临床疗效、子宫内膜厚度、子宫动脉血流及血清代谢组学的差异。结果：治疗后，观察组总有效率为95.00% （38/40），对照组为92.50% （37/40），组间比较，差异无统计学意义（P＞0.05）。治疗后，2 组内膜厚度均较治疗前增加（P＜0.05），且观察组内膜厚度大于对照组（P＜0.05）。治疗后，2组子宫动脉PI、RI、S/D值均较治疗前降低（P＜0.05），且观察组3项指标值均低于对照组（P＜0.05）。将IUA患者（对照组10例+观察组10例） 血清与正常人群（10例） 的血清进行代谢组学分析，结果显示，IUA患者较正常人群存在62个差异代谢物（P＜0.05），其中43个代谢物表达上调，19个代谢物表达下调。进一步分析显示，4-羟基-5-苯基戊酸-O-硫酸盐、维吉尼亚霉素M1、1-磷酸鞘氨醇、磷脂酰胆碱（13，5-二甲基脂肪酸/前列腺素E1） 在对照组治疗后表达明显上调；缬氨酸-甜菜黄素、白三烯D4、双姜黄酮环氧化物在对照组治疗后表达明显下调。缬氨酸-甜菜黄素、环（精氨酸-甘氨酸-天冬氨酸-D-苯丙氨酸-缬氨酸）（简称RGDfV环肽） 在观察组治疗后表达明显下调。京都基因与基因组百科全书（KEGG） 数据库分析显示，IUA相关异常代谢物主要涉及脂肪代谢及氨基酸代谢等途径；通路富集分析显示，异常代谢物主要集中于神经活性配体-受体相互作用和甘油磷脂代谢通路。结论：应用芬吗通、阿司匹林或在其基础上联用中药加减芎归补中汤治疗IUA术后患者，均可有效改善其临床症状，增加子宫内膜厚度及改善子宫动脉血流，中西医联合治疗效果更佳；IUA患者较正常人群存在差异代谢物，IUA发病可能与脂肪代谢紊乱相关；加减芎归补中汤可能通过下调RGDfV环肽表达，达到促进血管新生、恢复内膜的效果。

Abstract:

Abstract：Objective：To observe the clinical efficacy of modified Xionggui Buzhong Decoction in the treatment of patients with intrauterine adhesions （IUA） of qi deficiency and blood stasis type after hysteroscopic transcervical resection of adhesions （TCRA） based on metabolomics. Methods：A total of 80 patients with IUA of qi deficiency and blood stasis type who underwent TCRA at Yiwu Maternity and Children Hospital from April 2023 to December 2024 were randomly divided into the control group and the observation group using the random number table method，with 40 cases in each group. The control group received Estradiol Tablets/Estradiol and Dydrogesterone Tablets and Aspirin，while the observation group received modified Xionggui Buzhong Decoction in addition to the treatment given to the control group. Both groups were treated continuously for three months. The clinical efficacy， changes in endometrial thickness， uterine artery blood flow parameters，and serum metabolomics were compared between the two groups. Results：After treatment， the total effective rate was 95.00% （38/40） in the observation group and 92.50% （37/40） in the control group， with no statistically significant difference between the two groups （P＞0.05）. After treatment， endometrial thickness increased in both groups compared with that before treatment （P＜0.05），and the endometrial thickness in the observation group was greater than that in the control group （P＜0.05）. After treatment，the uterine artery pulsatility index （PI）， resistance index （RI）， and systolic/diastolic （S/D） ratio decreased in both groups compared with those before treatment （P＜0.05）， and the uterine artery PI， RI， and S/D ratio were lower in the observation group than those in the control group （P＜0.05）. Metabolomics analysis comparing serum of IUA patients （10 cases in the control group and 10 cases in the observation group） with that of healthy controls （10 cases） revealed 62 differential metabolites （P＜0.05）， of which 43 were upregulated and 19 were downregulated in IUA patients. Further analysis showed that 4-hydroxy-5（phenyl）- valeric acid-O-sulphate， virginiamycin M1， sphingosine-1-phosphate， and phosphatidylcholine （13， 5 dimethyl fatty acid/prostaglandin E1） were significantly upregulated in the control group after treatment； while valine-betaxanthin， leukotriene D4， and bisacurone epoxide were significantly downregulated in the control group after treatment. Valine-betaxanthin and cyclo（arginine-glycine-aspartic acid-D-phenylalaninevaline， short as RGDfV cyclic peptide） were significantly downregulated in the observation group after treatment. Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis indicated that IUA-related differential metabolites were primarily involved in lipid metabolism and amino acid metabolism pathways. Pathway enrichment analysis showed that the differential metabolites were mainly concentrated in the neuroactive ligandreceptor interaction and glycerophospholipid metabolism pathways. Conclusion： Treatment with Estradiol Tablets/Estradiol and Dydrogesterone Tablets and Aspirin， either alone or combined with modified Xionggui Buzhong Decoction， can effectively improve clinical symptoms， increase endometrial thickness， and improve uterine artery blood flow in IUA patients after TCRA. The integration of traditional Chinese and western medicine yields certain outcomes. Patients with IUA exhibit distinct metabolomic profiles compared with healthy individuals， and the pathogenesis of IUA may be associated with lipid metabolism disorders. Modified Xionggui Buzhong Decoction may promote angiogenesis and endometrial recovery by downregulating the expression of the RGDfV cyclic peptide.