摘要
目的观察利福昔明对慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)大鼠肝脏和肠黏膜屏障的保护作用。方法24只Wistar大鼠随机分为利福昔明干预组(RIF组)、ACLF组、正常对照组(Con组)。Con组予以生理盐水腹腔内注射,RIF组和ACLF组予以40%CCl_(4)橄榄油溶液进行造模;8周后RIF组加用利福昔明灌胃,两组大鼠继续CCl_(4)腹腔注射2周后予腹腔注射脂多糖,24 h后处死全部大鼠,取血清进行TB、ALT、AST、DAO、ET检测,并取肝组织和回肠组织进行病理检查及肠黏膜occludin蛋白检测。结果RIF组的血清TB、ALT、AST、DAO、ET水平低于ACLF组,差异有统计学意义(P<0.01)。ACLF组和RIF组肝脏外观均较Con组有肝脏缩小硬化表现。光镜下显示两组均有肝组织结构破坏,肝细胞坏死和炎性细胞浸润,但两组差别不明显。RIF组和ACLF组均有小肠绒毛变形、水肿、缩短、间距变宽、上皮细胞排列不整等现象;但RIF组程度较轻。与Con组比较,RIF组和ACLF组均有occludin蛋白表达减少,但在RIF组的表达高于ACLF组,差异有统计学意义(P<0.05)。结论利福昔明对CCl_(4)联合脂多糖诱导的ACLF大鼠有减轻肝损伤和保护肠黏膜的作用。
Objective To explore the protective effect of Rifaximin on liver and intestinal mucosal barrier in rats with acute-on-chronic liver failure(ACLF).Methods A total of 24 male Wistar rats were randomly(random number)divided into 3 groups:Rifaximin intervention group(RIF group,n=8),ACLF group(ACLF,n=8)and control group(Con group,n=8).The rats in the Con group were injected intraperitoneally with saline daily.The rats in the ACLF group and RIF group were injected intraperitoneally with 40%CCl_(4) olive solution for 8 weeks.In the beginning of the ninth week,the rates in the RIF group were given Rifaximin respectively.The carbon tetrachloride olive solution was still given to the rats in these two groups in the next two weeks.At the end the tenth weeks,the rats in the ACLF group and RIF group were injected intraperitoneally with lipopolysaccharide.All rats were sacrificed 24 hours later.The plasma levels of TB,ALT,AST,DAO and ET were measured.The pathological changes of liver and ileum tissue were observed by HE staining.The expression of occludin was detected.Results Compared with ACLF group,the serum levels of TB,ALT,AST,DAO,ET in the RIF group exist significant differences(P<0.01).The pathological results showed both ACLF group and RIF group presented disordered structure of liver,formation of pseudolobule and inflammatory cell infiltration in hepatic lobule without significant differences.The structure of small intestinal villi,mucosal space and other structures in the ACLF group were severely damaged,while the damages were slight in the RIF group.Compared with Con group,the expression of occludin protein in RIF group and ACLF group were decreased.The expression in RIF group was higher than that in ACLF group,and the difference was significant(P<0.01).Conclusion Rifaximin plays a protective role on the intestinal barrier and liver function in rats with ACLF induced by CCl_(4) and lipopolysaccharide.
作者
黄继英
沈曼茹
高振军
徐林芳
倪倩雯
HUANG Jiying;SHEN Manru;GAO Zhenjun;XU Linfang;NI Qianwen(Department of Gastroenterology,Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University,Shanghai 201700,China)
出处
《胃肠病学和肝病学杂志》
CAS
2023年第7期775-778,784,共5页
Chinese Journal of Gastroenterology and Hepatology
基金
上海市青浦区科学技术委员会基金项目(QKY2021-06)。
关键词
利福昔明
慢加急性肝衰竭
肠黏膜
肝脏保护
Rifaximin
Acute-on-chronic liver failure
Intestinal mucosa
Liver protection