摘要
背景:利福昔明可明显缓解肠易激综合征患者的腹痛,但机制不明。目的:探讨利福昔明对大鼠内脏敏感性的影响及其作用机制。方法:建立慢性避水应激大鼠模型,并将大鼠分为对照组、模型组和利福昔明组。行肌电图评估大鼠内脏敏感性,免疫荧光法检测L6S1 DRG中TRPV1、VGLUT2/3免疫活性,蛋白质印迹法检测L6S1段脊髓中TRPV1、VGLUT2/3蛋白表达,行16S rDNA菌群测序分析。结果:慢性避水应激能诱导大鼠内脏敏感性增高,L6S1 DRG中TRPV1、VGLUT2/3免疫活性明显增高,L6S1段脊髓中TRPV1、VGLUT2/3蛋白表达明显增高,肠道菌群发生紊乱。给予利福昔明后,内脏敏感性明显降低,L6S1 DRG中TRPV1、VGLUT2/3免疫活性明显降低,L6S1段脊髓中TRPV1、VGLUT2/3蛋白表达明显降低,肠道菌群紊乱明显改善。TRPV1拮抗剂可明显降低VGLUT2/3免疫活性。结论:利福昔明通过肠道菌群和TRPV1-VGLUT2/3通路改善应激诱导的大鼠内脏高敏感。
Background:Rifaximin has obvious effect on relieving abdominal pain in patients with irritable bowel syndrome,but the mechanism is not clear.Aims:To investigate the effect and mechanism of rifaximin on visceral sensitivity in rats.Methods:Chronic water avoidance stress(WAS)model was established in rats,and rats were divided into control group,WAS group and rifaximin group.Electromyogram was used to evaluate the visceral sensitivity.Immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG were determined by immunofluorescence,protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were determined by Western blotting.Bacterial 16S rDNA sequencing analysis for intestinal flora was performed.Results:WAS could induce visceral hyperalgesia in rats,immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG were significantly increased,protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were significantly increased,and imbalance of intestinal flora was induced.Rifaximin could ameliorate visceral hyperalgesia;immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG and protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were significantly decreased;imbalance of intestinal flora was ameliorated.TRPV1 antagonist could significantly decrease the immunological activities of VGLUT2/3.Conclusions:Rifaximin can ameliorate the visceral hyperalgesia induced by WAS via intestinal flora and TRPV1-VGLUT2/3 pathway.
作者
杨长青
郭晓姝
李季
赵莉
赵甘婷
盛淑婷
魏子白
YANG Changqing;GUO Xiaoshu;LI Ji;ZHAO Li;ZHAO Ganting;SHENG Shuting;WEI Zibai(Department of Gastroenterology,Peace Hospital Affiliated to Changzhi Medical College,Changzhi,Shanxi Province,046000)
出处
《胃肠病学》
2019年第11期650-654,共5页
Chinese Journal of Gastroenterology
基金
国家自然科学基金(81600422)