柴胡加龙骨牡蛎汤对2型糖尿病合并抑郁患者肠道菌群的影响

目的观察柴胡加龙骨牡蛎汤联合黛力新对2型糖尿病合并抑郁患者肠道菌群的影响。方法选取2型糖尿病合并抑郁患者共计86例，随机分为试验组和对照组，每组43例。对照组予口服氟哌噻吨美利曲辛片（黛力新）治疗，每日2次，早晨及中午各1片；试验组予黛力新联合柴胡加龙骨牡蛎汤，中药每日2次，每次1袋。干预疗程均为8周。比较两组治疗前后空腹血糖（FPG）、餐后血糖（2hPG）、糖化白蛋白（GA）、白细胞介素-6（IL-6）、C反应蛋白（CRP）、五羟色胺（5-HT）、汉密尔顿抑郁量表（HAMD-17）评分、抑郁自评量表（SDS）评分、中医证候评分的变化，通过16s rDNA高通量测序对肠道菌群OUT数量、多样性指数及差异菌群进行综合分析和评价。结果最终纳入统计80例患者，试验组和对照组各40例。与本组治疗前比较，治疗后两组患者的FPG、2hPG、GA、IL-6、CRP水平均降低（P＜0.05），5-HT水平升高（P＜0.05），其中试验组GA、IL-6、CRP、5-HT的改善程度明显优于对照组（P＜0.05）。与对照组治疗后比较，试验组HAMD-17评分、中医证候积分均降低（P＜0.05）。Alpha多样性分析显示，治疗后试验组Shannon指数、Chao指数、Ace指数均升高（P＜0.05），Simpson指数降低（P＜0.05）。Beta多样性分析显示，治疗后试验组患者肠道微生物群落的分布位置和象限区间较基线发生明显变化。LefSe差异分析显示，试验组治疗前后有4个差异菌门、7个差异菌科、9个差异菌属，与对照组同期相比主要表现为厚壁菌门（Firmicutes）丰度上调，变形菌门（Proteobacteria）、拟杆菌门（Bacteroidetes）丰度下调。结论柴胡加龙骨牡蛎汤能够有效改善2型糖尿病合并抑郁患者的临床症状，其机制可能与下调炎症细胞因子水平、上调5-HT浓度以及调节肠道菌群有关。

英文摘要:

Objective To observe the effects of Chaihu plus Longgu Muli Decoction（CLMD） on intestinal microflora structural characteristics of patients with type 2 diabetes mellitus complicated with depression. Methods A total of 86 patients with type 2 diabetes mellitus complicated with depression were randomly divided into the experimental group and control group， with 43 patients in each group. The control group was orally treated with flupentixol melitracen tablets （Deanxit），twice a day，one tablet in the morning and one tablet at noon，the experimental group received Deanxit combined with CLMD twice a day，one bag each time. The intervention course remained 8 weeks. The changes of fasting blood glucose（FPG），postprandial blood glucose（2hPG），glycated albumin（GA），interleukin-6（IL-6），C-reactive protein（CRP），Hamilton Depression Scale（HAMD-17） score ，Self-Rating Depression Scale（SDS） score and Chinese medicine（CM） syndrome score were compared between the two groups before and after treatment. The OUT number，diversity index and differential flora of intestinal flora were comprehensively analyzed and evaluated by 16S rDNA high-throughput sequencing. Results Compared with before treatment，the levels of FPG，2hPG，GA，IL-6 and CRP in two groups significantly decreased after treatment（P＜0.05），5-HT level increased（P＜0.05），the improvement degree of GA，IL-6，CRP and 5-HT in the experimental group was better than those in control group（P＜0.05）. Compared with the control group after treatment，HAMD-17 score and CM syndrome score of experimental group significantly decreased（P＜0.05）. Alpha diversity analysis showed that Shannon index，Chao index and Ace index increased significantly after treatment（P＜0.05）， Simpson index significantly decreased（P＜0.05）. Beta diversity analysis showed that after treatment，the distribution location and quadrant range of intestinal microflora in the experimental group changed significantly compared with the baseline. LefSe difference analysis showed that there were 4 differentially divided phyla，7 differentially divided families and 9 differentially divided genera in the experimental group before and after treatment. Compared with the control group at the same time，the abundance of Firmicutes was mainly increased. The abundance of Proteobacteria and Bacteroidetes decreased. Conclusion CLMD can effectively improve the clinical symptoms of type 2 diabetes patients with depression，and the mechanism may be related to down-regulation of inflammatory cytokines，up-regulation of 5-HT concentration and regulation of intestinal microflora structure.

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