ω-3多不饱和脂肪酸对急性肝功能衰竭小鼠肝细胞保护机制研究  

Study on the protective mechanism ofω-3 polyunsaturated fatty acids on the hepatocytes in mice with acute liver failure

作　　者：张玉荣 李高峰 汤彦 章美元 ZHANG Yurong;LI Gaofeng;TANG Yan;ZHANG Meiyuan(Department of Emergency,Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University,Shanghai 201700,China)

机构地区：[1]复旦大学附属中山医院青浦分院急诊科,上海201700

出　　处：《长春中医药大学学报》2023年第6期637-642,共6页Journal of Changchun University of Chinese Medicine

基　　金：蚌埠医学院自然科学类项目(BYKY201926IZD);2019-2022年上海市医学重点专科建设项目(ZK2019B07)。

摘　　要：目的 探索ω-3多不饱和脂肪酸(3-PUFA)对急性肝功能衰竭小鼠模型的肝细胞保护机制,为临床重症肝病的免疫营养治疗提供理论依据。方法 取100只小鼠,空白组8只未采取任何措施干预,其余92只采取D-氨基半乳糖(D-GaIN)联合脂多糖(LPS)诱导急性肝衰竭小鼠(BALB/C)造模,分成4组,未干预的模型组20只,用3-PUFA干预24只,以乌司他丁和促肝细胞生长素分别为阳性药物对照组,各24只,干预后6、12、24 h检测并比较各组小鼠相应血清炎症指标、肝功能的酶学、肝组织中microRNA-122a和肝脏组织病理学变化。结果 造模后,未干预前小鼠累计死亡18只,干预后6、12、24 h获得血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、降钙素原(PCT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆碱酯酶(CHE)、microRNA-122a和相应病理学结果,3-PU FA组、乌司他丁组和促肝细胞生长素组均表现为炎症指标的下降和microRNA-122a表达下降,均与模型组比较差异显著(P <0.05)。在组织病理学方面,模型组炎症程度随着时间推移逐步加重,大量浆细胞浸润和炎性渗出,3组干预后,促肝细胞生长素组炎症减退和浆细胞浸润减少最明显,3-PUFA组、乌司他丁组的结果相似。结论 3-PUFA可能通过调节microRNA-122a表达对肝细胞起到抗炎、修复作用,具有免疫营养的潜在价值。Qbjective To explore the protective mechanism ofω-3 polyunsaturated fatty acids(3-PUFA)on the hepatocytes in mice with acute liver failure,and provide the theoretical basis for immunonutritional treatment of severe hepatopathy.Methods A total of 100 mice were selected,including 8 mice in the blank group without any intervention,and 92 mouse model(BALB/C)of the acute liver failure induced by D-galactosamine(D-GaIN)combined with lipopolysaccharide(LPS).The mice were divided into the model group without intervention(n=24),the 3-PUFA intervention group(n=24),the positive drug control groups[ulinastatin group(n=24)and hepatocellular growth promoting hormone(HGHP)group(n=24)].At 6h,12h,24h after the intervention,the corresponding serum inflammatory indicators,liver function enzymology,microRNA-122a in liver tissue and liver histopathological changes were monitored and compared in each group.Results After molding,18 mice died without intervention.Serum tumor necrosis factor(TNF-a),interleukin-6(IL-6),calcitonin(PCT),alanine transaminase(ALT),aspartate transaminase(AST),cholinesterase(CHE),microRNA-122a and the liver histopathological results were obtained at 6h,12h,24h after the intervention.The 3-PUFA group,ulinastatin group and HGHP group showed a decline in inflammatory indicators and the microRNA-122a expression,which were significantly differences from the model group(P<0.05).In terms of liver histopathology,the degree of inflammation in the model group gradually increased over time,with a large number of plasmic cell infiltration and inflammatory exudation.After the intervention of the three groups,the decrease of inflammation and plasma cell infiltration in HGHP group was the most obvious,and the results of the 3-PUFA group and the ulinastatin group were similar.Conclusion 3-PUFA may have anti-inflammatory and repair effects on the hepatocytes by regulating the expression of microrNA-122a,and has the potential value of immune nutrition.

关 键 词：小鼠 急性肝功能衰竭 Ω-3多不饱和脂肪酸 保护作用 

分 类 号：R575[医药卫生—消化系统]