摘要
目的观察骨髓间充质干细胞(BMSCs)对肝硬化大鼠肠道菌群的影响。方法2019年3月至9月,选取115只SD大鼠(军事医学科学院实验动物中心提供)腹腔注射四氯化碳(CCL4)建立肝硬化模型后,采用随机数表法分组方式分为模型组、BMSCs组及小檗碱组,分别注射磷酸缓冲盐溶液(PBS)、BMSCs及小檗碱灌胃处理,另选取10只大鼠作为对照组,干预后处死各组大鼠,苏木精-伊红(HE)及天狼星红染色检测肝脏组织病理学改变,生化分析仪检测血清白蛋白(ALB)与总胆红素(TBIL),酶联免疫吸附测定法(ELISA)检测血清层黏连蛋白(LN)含量变化;采集各组大鼠粪便标本,对细菌16S rDNA基因V3~V4区进行聚合酶链式反应(PCR)扩增,并进行高通量测序,两组间数据比较采用独立样本t检验,3组数据间比较采用单因素方差分析。结果BMSCs组大鼠肝组织Ishak评分及分期[(4.00±0.63)分、4.50±0.55]均低于模型组[(7.83±0.75)分、5.83±0.41],差异有统计学意义(t=3.833、1.333,P<0.05);BMSCs组大鼠血清ALB含量[(29.65±1.38)g/L]高于模型组[(22.76±2.67)g/L],差异有统计学意义(t=6.882,P<0.05);TBIL及LN的含量[(3.09±0.25)μmol/L、(45.19±1.86)ng/ml]均低于模型组[(10.75±1.14)μmol/L、(56.69±2.00)ng/ml],差异有统计学意义(t=7.658、11.497,P<0.05);BMSCs组大鼠肠道菌群中脱硫弧菌科及脱硫弧菌属丰度明显高于模型组,梭菌科及梭状芽胞菌属丰度明显低于模型组。结论BMSCs移植治疗可以有效改善肝硬化大鼠的肝功能及肝纤维化程度,其机制可能与调节其肠道菌群有关。
Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on intestinal flora in cirrhotic rats.Methods From March to September 2019,115 sprague-dawley(SD)rats(provided by Experimental Animal Center of Military Medical Science Academy,China)were selected to establish liver cirrhosis models by intraperitoneal injection of carbon tetrachloride(CCl4),and randomly divided into model group,BMSCs group and berberine group.Phosphate buffer saline(PBS),BMSCs and berberine were given by injection or gavage respectively.A total of 10 rats were selected as control group.After intervention,rats in each group were executed,and liver histopathology was observed by hematoxylin and eosin(HE)and Sirius red staining.Serum albumin(ALB),total bilirubin(TBIL)and laminin(LN)were determined by biochemical analyzer or enzyme linked immunosorbent assay(ELISA).Intestinal flora DNA was extracted from fecal samples and the V3-V4 variable region of 16S rDNA was amplified.T-test was used to compare the data between the two groups,and one-way ANOVA was used to compare the data among three groups.Results Ishak scores and stage[(4.00±0.63)points,4.50±0.55]in BMSCs group were significantly lower than in model group[(7.83±0.75)points,5.83±0.41,t=3.833,1.333,P<0.05],serum ALB,TBIL and LN levels[(29.65±1.38)g/L,(3.09±0.25)μmol/L,(45.19±1.86)μg/L]were significantly increased or decreased as compared with model group[(22.76±2.67)g/L,(10.75±1.14)μmol/L,(56.69±2.00)μg/L,t=6.882,7.658,11.497,P<0.05],and the abundance of desulfovibrionaceae and desulfovibrio increased,while clostridiaceae and clostridium decreased.Conclusion BMSCs can improve liver function and alleviated liver fibrosis in cirrhotic rats possibly through regulating the intestinal flora.
作者
翟浩宇
曹欢
杨柳
宋红丽
Zhai Haoyu;Cao Huan;Yang Liu;Song Hongli(First Central Clinical College,Tianjin Medical University,Tianjin 300070,China;Department of Organ Transplantation,Tianjin First Central Hospital,Tianjin 300192,China)
出处
《中华实验外科杂志》
CAS
北大核心
2021年第4期659-661,共3页
Chinese Journal of Experimental Surgery
基金
国家自然基金面上项目(81670574、81441022、81270528)。
关键词
肝硬化
骨髓间充质干细胞
小檗碱
肠道菌群
Liver cirrhosis
Bone marrow mesenchymal stem cells
Berberine
Intestinal flora
