补中益气汤治疗直肠脱垂的作用机制研究:基于手术切除标本的单细胞转录组测序相关分析  

Study on the mechanism of Buzhong Yiqi Decoction in the treatment of rectal prolapse: related analysis of single-cell transcriptome sequencing based on surgical excision specimens

作　　者：陈华显[1] 肖国中 刘访 林宏城[1] Chen Huaxian;Xiao Guozhong;Liu Fang;Lin Hongcheng(Department of Colorectal Surgery,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,Guangdong,China)

机构地区：[1]中山大学附属第六医院肛肠外科,广东广州510655

出　　处：《结直肠肛门外科》2023年第1期38-46,共9页Journal of Colorectal & Anal Surgery

基　　金：国家自然科学基金面上项目(82174369);广东省自然科学基金面上项目(2020A1515011254);广东自然科学基金杰出青年项目(2022B1515020003)。

摘　　要：目的 使用补中益气汤联合手术治疗直肠脱垂有较好的临床疗效,但补中益气汤的作用机制尚不明确,初步探讨补中益气汤治疗直肠脱垂的分子机制。方法 回顾性分析2018年1月至2022年9月在中山大学附属第六医院肛肠外科接受经会阴手术治疗的30例直肠脱垂患者的临床资料。将10例服用过补中益气汤者作为治疗组;使用倾向性匹配评分方法,根据年龄和性别匹配20例仅接受经会阴手术治疗的直肠脱垂患者作为对照组。对比分析两组临床指标。两组各择定1例患者作为分析样本来源对象,进行单细胞转录组测序相关分析。结果 治疗组的治疗有效率为100%,对照组相应为80%。治疗后,治疗组的Longo ODS评分低于同期的对照组(P=0.034)。两组治疗前后Longo ODS评分差值、Wexner肛门失禁评分差值比较差异均有统计学意义(P=0.030、P=0.046)。通过单细胞转录组测序相关分析发现:与对照组相比,治疗组的成纤维细胞比例更高,治疗组的成纤维细胞促进细胞外基质形成、抑制细胞外基质降解的功能更显著。两组成纤维细胞、平滑肌细胞的转录组存在差异,涉及多种基因及其相关通路,可能与细胞生物学行为、细胞功能、细胞活性有关;平滑肌细胞、周细胞与成纤维细胞通过PDGF-PDGFR配受体对进行互作,治疗组的这一配受体对的表达高于对照组。结论 对于直肠脱垂患者,在手术前予以补中益气汤治疗可提高总体疗效。补中益气汤的作用机制可能是促进细胞外基质合成及抑制细胞外基质降解,其中成纤维细胞扮演了重要的角色。Objectives Buzhong Yiqi Decoction combined with surgery has good clinical efficacy in the treatment of rectal prolapse, but the mechanism of Buzhong Yiqi Decoction is not clear. This is a preliminary study to investigate the molecular mechanism of Buzhong Yiqi Decoction in the treatment of rectal prolapse. Methods The clinical data of 30 patients with rectal prolapse who underwent transperineal surgery at Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University from January 2018 to September 2022 were retrospectively analyzed. 10 patients who had taken Buzhong Yiqi decoction were selected as the treatment group. 20 patients who received transperineal surgery only were matched according to age and sex using propensity matching scoring method as the control group. The clinical indicators of the two groups were compared and analyzed. One patient in each group was selected as the sample source for analysis, and the related analysis of single-cell transcriptome sequencing was performed. Results The effective rate was 100% in the treatment group and 80% in the control group. After treatment, Longo ODS score in the treatment group was lower than that in the control group(P=0.034). The two groups differ significantly regarding the change in Longo ODS score and Wexner anal incontinence score before and after treatment(P=0.030,P=0.046). Related analysis of single-cell transcriptome sequencing showed that compared with the control group, the proportion of fibroblasts in the treatment group was higher, and the function of fibroblasts in the treatment group was more significant in promoting the formation of extracellular matrix and inhibiting the degradation of extracellular matrix. There are differences in the transcriptome of fibroblasts and smooth muscle cells between the two groups, involving a variety of genes and their related pathways, which may be related to cell biological behavior, cell function and cell activity. Smooth muscle cells and pericytes interact fibroblasts through PDGF-PDGF

关 键 词：直肠脱垂 补中益气汤 手术治疗 单细胞转录组测序 分子机制 

分 类 号：R574.63[医药卫生—消化系统]