细胞角蛋白18片段和内毒素血症在单纯性脂肪肝转化为非酒精性脂肪性肝炎中的促进作用

来源 :The 14th Congress of Gastroenterology China(第十四届全国消化系病学术会议) | 被引量 : 0次 | 上传用户:YNiit562552379
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  目的 探讨细胞角蛋白18(CK18)、内毒素血症在非酒精性脂肪性肝病(NAFLD)发生中的作用,以及肥胖与NAFLD之间存在的关联.方法 将38只大鼠分为正常对照、单纯性脂肪肝(NAFL)、非酒精性脂肪性肝炎(NASH)和单纯性肥胖组.造模成功后,ELISA法检测前3组血清中CK18(M30)片段,自动生物化学仪测定各组血清转氨酶,动态比浊法测定血清内毒素水平,ELISA检测血清IL-18,RT-PCR分析肠道粪便中肠道菌群的改变,取肝脏和末端回肠标本HE染色,光学显微镜下观察病理学变化.结果 NASH组大鼠血清中CK-18(M30)显著高于正常对照组和NAFL组,而NAFL组与正常对照组差异无统计学意义.CK-18片段与肝脏炎症活动度、ALT、AST、IL-18和内毒素均呈正相关,而与肝脏脂肪变性无关.NASH组大鼠大肠埃希菌属数量、ALT、AST、IL-18、内毒素、TC、TG、空腹血糖均显著高于其余组,而乳酸杆菌属、双歧杆菌属数量均显著低于其余组.NAFL组与单纯性肥胖组大肠埃希菌属数量、TC、TG、空腹血糖和内毒素均高于正常对照组,而乳酸杆菌、双歧杆菌属数量均低于正常对照组.NAFL组大肠埃希菌数、内毒素高于单纯性肥胖组,双歧杆菌数低于单纯性肥胖组,而乳酸杆菌数、TC、TG、空腹血糖、IL-18、ALT和AST差异无统计学意义.内毒素与大肠埃希菌、IL-18、ALT、AST均呈正相关,而与乳酸杆菌属呈负相关,与双歧杆菌无关.正常对照组可见小肠黏膜表面微绒毛排列整齐,相邻细胞间细胞连接结构清晰.从单纯性肥胖组、NAFL组到NASH组,可见肠道黏膜屏障和间质炎性反应由轻到重的变化.结论 NASH血清中CK-18(M30)可作为NASH评判和预测的独立因素.肠道菌群紊乱可能是单纯性肥胖进展为NAFLD的高危因素.NAFLD早期存在肠源性内毒素血症,可能是促进肝脏损伤的病因,肠道屏障的损伤可能是促使内毒素升高的始动因素,肠源性内毒素又可引发肝内炎性反应,导致NASH的发生.
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