Xu Hong, Xiong Jingfang, Xu Jianjun, Li Shuiming, Zhou Yang, Chen Dongya, Cai Xinjun, Ping Jian, Deng Min, Chen Jianyong
Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China.
Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, China.
Dig Dis Sci. 2017 Oct;62(10):2801-2811. doi: 10.1007/s10620-017-4704-x. Epub 2017 Aug 16.
Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats.
A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting.
Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1.
Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.
肠道动力受损可能导致肠道微生物群平衡破坏，进而促进肝硬化患者的细菌移位（BT）和内毒素血症。我们评估了促动力药莫沙必利对肝硬化大鼠BT及肠道微生物群DNA指纹图谱的影响。
通过皮下注射四氯化碳（CCl）建立大鼠肝硬化模型。测定肝硬化大鼠的门静脉压力、肝脏和肠道损伤、血浆内毒素、BT及肠道转运率（ITR）。通过ERIC-PCR获得粪便DNA指纹图谱。采用蛋白质免疫印迹法评估紧密连接蛋白的表达。
莫沙必利治疗肝硬化大鼠可显著降低血浆内毒素水平和BT发生率，并伴有ITR增加。发生BT的肝硬化大鼠（包括接受莫沙必利治疗的大鼠）的ITR显著低于未发生BT的大鼠。Pearson系数表明血浆内毒素水平与ITR之间存在显著负相关。三组肠道微生物群的基因组指纹图谱分为三个不同的簇。与模型组相比，莫沙必利治疗组的香农指数显著增加。香农指数与ITR之间存在显著正相关。莫沙必利未改善肝脏和肠道损伤以及回肠中闭合蛋白和ZO-1的表达。
莫沙必利可显著增加肝硬化大鼠的肠道动力，从而恢复紊乱的肠道微生物群，最终降低血浆内毒素水平和BT发生率。
