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作 者:姚童 李锐 陈鹏 YAO Tong;LI Rui;CHEN Peng(Department of Pathophysiology,School of Basic Medical Sciences,Southern Medical University)
机构地区:[1]南方医科大学基础医学院病理生理学教研室,广州510515
出 处:《中国科学:生命科学》2023年第5期736-745,共10页Scientia Sinica(Vitae)
基 金:国家自然科学基金(批准号:32071124)资助。
摘 要:肝脏缺血再灌注损伤(hepatic ischemia reperfusion,HIRI)是机体休克或肝脏外科手术术后重要并发症.肠道菌群在肝损伤中起着至关重要的作用,但目前其对HIRI的调控研究还处于起步阶段.为了深入探究HIRI与肠道菌群的直接联系,本课题组研究了具体肠道共生菌灵巧粪球菌(Coprococcus catus,C.catus)对HIRI的潜在贡献.本研究建立小鼠肝脏缺血再灌注损伤模型,并通过抗生素清除小鼠肠道菌群,氯磷酸二钠脂质体注射清除小鼠巨噬细胞.结果显示,清除革兰氏阳性细菌可加剧小鼠HIRI,肠道革兰氏阳性共生菌——C.catus可改善肝脏缺血再灌注引起的肝损伤.此外,巨噬细胞清除后,C.catus的保护效应削弱很多,但仍显示一定保护HIRI的趋势.本研究发现了一种新的可以保护小鼠肝脏缺血再灌注损伤的肠道革兰氏阳性厌氧细菌——C.catus,该菌可部分依赖于巨噬细胞缓解肝脏缺血再灌注引发的炎症反应及肝损伤.Hepatic ischemia reperfusion injury(HIRI)is a common complication after shock or liver surgery.The gut microbiota plays an important role in liver injury,but the relationship between gut microbiota and HIRI has not been fully understood.In order to further explore the detail contribution of gut microbiota to HIRI,here we studied the potential effect of intestinal symbiotic bacteria(Coprococcus catus,C.catus)on HIRI progression in mice.We established mice HIRI model(70%liver blood flow was restricted for90 min,followed by 6 h reperfusion)and mice were gavaged with narrow-spectrum antibiotics to deplete gut microbiota.Clodronate liposomes were employed to deplete macrophages in vivo.Our results showed that HIRI was exacerbated after the depletion of grampositive bacteria,but this phenomenon did not occur in the depletion of gram-negative bacteria.In addition,the intestinal grampositive commensal bacteria(C.catus)can improve HIRI in mice.Compared with C.catus culture supernatant,inactivated C.catus displayed a significant improvement of HIRI.Furthermore,C.catus still showed a certain tendency to protect HIRI in macrophagecleared mice.In this study,we reported the beneficial effects of a new strain of intestinal gram-positive anaerobe-C.catus against HIRI in mice.C.catus may partially rely on macrophages to relieve inflammation and liver damage during HIRI.
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