舒林酸联合双歧杆菌三联活菌治疗家族性腺瘤性息肉病的作用及其机制初探

目的探讨舒林酸联合双歧杆菌三联活菌(培菲康)治疗家族性腺瘤性息肉病(FAP)的疗效及其机制。 方法收集2013年1月1日至2022年1月1日在上海交通大学医学院附属瑞金医院就诊的FAP患者，采用随机数字表法，将经胃肠镜检查及组织病理学检查确诊的这些FAP患者，分为舒林酸组、培菲康组、舒林酸联合培菲康组3组。舒林酸组口服舒林酸400 mg/d，疗程为1年；培菲康组口服培菲康6粒/d，疗程1年；舒林酸联合培菲康组，口服舒林酸400 mg/d+6粒培菲康/d，疗程1年。每4个月结肠镜复查1次，观察每组患者一般情况，腺瘤的病理类型、大小、数目。采用16sRNA高通量测序分析患者粪便菌群变化Western blot检测凋亡抑制蛋白Bcl-2的表达。 结果入组患者共90例，每组30例，舒林酸联合培菲康组于治疗后4、8、12个月腺瘤的病理类型：管状腺瘤分别占活检腺瘤总数分别为90.5%、94.4%、99.2%；绒毛管状腺瘤占9.5%、5.6%、0.8%；舒林酸组分别为85.3%、90.4%、95.2%，培菲康组分别为80.5%、85.3%、90.2%。舒林酸+培菲康组与培菲康组、舒林酸组比较，差异有统计学意义(P<0.05)16sRNA测序提示舒林酸联合培菲康组厚壁菌门和放线菌门比例增加，而拟杆菌门比例降低。Western blot显示舒林酸联合培菲康组Bcl-2表达显著较其它组降低(P<0.05)。 结论舒林酸联合培菲康能有效的治疗FAP，其疗效优于单纯服用舒林酸组和培菲康组。可能的机制与降低Bcl-2，减少对凋亡的抑制，促进了腺瘤的凋亡，同时改善了肠内环境菌群有关。

Effect and its mechanism of sulinic acid combined with bifidobacterium triplex live bacteria on familial adenomatous polyposis

ObjectiveTo investigate the efficacy and mechanism of sulinic acid combined with bifidobacterium triplex live bacteria(bifico)in the treatment of familial adenomatous polyposis(FAP). MethodsFAP patients admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 1, 2013 to January 1, 2022 were collected.These FAP patients confirmed by gastroenteroscopy and histopathology were divided into 3 groups by random number table method: sulinic acid group, bifico group and sulinic acid combined with bifico group.The sulinic acid group received sulinic acid 400 mg/d orally for 1 year.Bifico group received bifico 6 capsules/d for 1 year.The sulinic acid combined with bifico group received 400 mg/d of sulinic acid and 6 capsules/d of bifico for 1 year.Colonoscopy was performed once every 4 months to observe the general situation, pathological type, size and number of adenoma in each group.16sRNA high-throughput sequencing was used to analyze the changes of intestinal flora.Western blotting was used to detect the expression of apoptosis suppressor protein Bcl-2. ResultsA total of 90 patients were enrolled, 30 in each group.Pathological types of adenomas in sulinic acid combined with bifico group at 4, 8 and 12 months after treatment were as follows: tubular adenomas accounted for 90.5%, 94.4% and 99.2% of the total biopsy adenomas, respectively.Tubulovillous adenomas accounted for 9.5%, 5.6% and 0.8%; 85.3%, 90.4%, 95.2% in the sulinic acid group and 80.5%, 85.3%, 90.2% in the bifico group, respectively.Compared with the bifico group and sulinic acid group, there was a statistically significant difference(P<0.05).According to 16sRNA sequencing, the proportion of firmicutes and actinomycetes increased in sulinic acid combined with bifico group, while the proportion of bacteroidetes decreased.Western blotting showed that the expression of Bcl-2 in the sulinic acid combined with bifico group was significantly higher than that in other groups(P<0.05). ConclusionSulinic acid combined with bifico can effectively treat FAP, and its efficacy is better than that of sulinic acid and bifico alone.The possible mechanism may be related to the decrease of Bcl-2, the reduction of inhibition of apoptosis, the promotion of adenoma apoptosis, and the improvement of intestinal microflora.