实用肝脏病杂志
實用肝髒病雜誌
실용간장병잡지
JOURNAL OF CLINICAL HEPATOLOGY
2014年
6期
615-618
,共4页
徐正婕%李楠%何崇信%范建高
徐正婕%李楠%何崇信%範建高
서정첩%리남%하숭신%범건고
非酒精性脂肪性肝病%代谢性内毒素血症%高脂饮食%4型Toll样受体%小鼠
非酒精性脂肪性肝病%代謝性內毒素血癥%高脂飲食%4型Toll樣受體%小鼠
비주정성지방성간병%대사성내독소혈증%고지음식%4형Toll양수체%소서
Nonalcoholic fatty liver disease%Metabolic endotoxemia%High-fat diet%Toll-like receptor 4%Mice
目的：观察持续4 w的模拟代谢性内毒素血症对小鼠肝脏组织病理和4型Toll样受体（TLR4）信号通路的影响。方法将30只雄性C57BL/6J 小鼠随机分为正常组（n=10）和内毒素组（n=10），均予以普通饲料喂养，和高脂组（n=10），予以高脂饲料喂养。内毒素组小鼠同时经腹部皮下植入的微泵注入内毒素300μg·kg-1·d-1，连续4 w，正常组小鼠皮下微泵持续注入生理盐水作为对照。4 w后测定小鼠血清内毒素水平，对肝组织切片行HE染色后进行非酒精性脂肪性肝病评分（NAS），采样Real time PCR法测定小鼠肝组织TLR4及其下游的MyD88和TRIF-related adaptor molecule （TRAM） mRNA水平。结果内毒素组小鼠血清内毒素水平（0.62±0.04 EU/ml）显著高于正常组（0.50±0.06 EU/ml，P<0.05）和高脂组（0.49±0.05 EU/ml，P<0.05）；内毒素组小鼠肝组织主要表现为单纯性脂肪变性，NAS积分为（2.30±0.49），高脂组小鼠肝组织炎症较明显，NAS积分为（4.20±1.61），显著高于内毒素组（P<0.05）；与正常组相比，内毒素组小鼠肝组织TLR4 mRNA 水平上调5.12倍（P＜0.01），TRAM mRNA水平上调3.46倍（P＜0.01），而MyD88 mRNA水平与正常组比，无显著差别。结论持续4 w的模拟代谢性内毒素血症可诱导小鼠肝脏单纯性脂肪变性，TLR4 mRNA 和TRAM mRNA水平上调，而MyD88 mRNA水平无显著变化。
目的：觀察持續4 w的模擬代謝性內毒素血癥對小鼠肝髒組織病理和4型Toll樣受體（TLR4）信號通路的影響。方法將30隻雄性C57BL/6J 小鼠隨機分為正常組（n=10）和內毒素組（n=10），均予以普通飼料餵養，和高脂組（n=10），予以高脂飼料餵養。內毒素組小鼠同時經腹部皮下植入的微泵註入內毒素300μg·kg-1·d-1，連續4 w，正常組小鼠皮下微泵持續註入生理鹽水作為對照。4 w後測定小鼠血清內毒素水平，對肝組織切片行HE染色後進行非酒精性脂肪性肝病評分（NAS），採樣Real time PCR法測定小鼠肝組織TLR4及其下遊的MyD88和TRIF-related adaptor molecule （TRAM） mRNA水平。結果內毒素組小鼠血清內毒素水平（0.62±0.04 EU/ml）顯著高于正常組（0.50±0.06 EU/ml，P<0.05）和高脂組（0.49±0.05 EU/ml，P<0.05）；內毒素組小鼠肝組織主要錶現為單純性脂肪變性，NAS積分為（2.30±0.49），高脂組小鼠肝組織炎癥較明顯，NAS積分為（4.20±1.61），顯著高于內毒素組（P<0.05）；與正常組相比，內毒素組小鼠肝組織TLR4 mRNA 水平上調5.12倍（P＜0.01），TRAM mRNA水平上調3.46倍（P＜0.01），而MyD88 mRNA水平與正常組比，無顯著差彆。結論持續4 w的模擬代謝性內毒素血癥可誘導小鼠肝髒單純性脂肪變性，TLR4 mRNA 和TRAM mRNA水平上調，而MyD88 mRNA水平無顯著變化。
목적：관찰지속4 w적모의대사성내독소혈증대소서간장조직병리화4형Toll양수체（TLR4）신호통로적영향。방법장30지웅성C57BL/6J 소서수궤분위정상조（n=10）화내독소조（n=10），균여이보통사료위양，화고지조（n=10），여이고지사료위양。내독소조소서동시경복부피하식입적미빙주입내독소300μg·kg-1·d-1，련속4 w，정상조소서피하미빙지속주입생리염수작위대조。4 w후측정소서혈청내독소수평，대간조직절편행HE염색후진행비주정성지방성간병평분（NAS），채양Real time PCR법측정소서간조직TLR4급기하유적MyD88화TRIF-related adaptor molecule （TRAM） mRNA수평。결과내독소조소서혈청내독소수평（0.62±0.04 EU/ml）현저고우정상조（0.50±0.06 EU/ml，P<0.05）화고지조（0.49±0.05 EU/ml，P<0.05）；내독소조소서간조직주요표현위단순성지방변성，NAS적분위（2.30±0.49），고지조소서간조직염증교명현，NAS적분위（4.20±1.61），현저고우내독소조（P<0.05）；여정상조상비，내독소조소서간조직TLR4 mRNA 수평상조5.12배（P＜0.01），TRAM mRNA수평상조3.46배（P＜0.01），이MyD88 mRNA수평여정상조비，무현저차별。결론지속4 w적모의대사성내독소혈증가유도소서간장단순성지방변성，TLR4 mRNA 화TRAM mRNA수평상조，이MyD88 mRNA수평무현저변화。
Objective To observe the influence of 4-week mimic metabolic endotoxemia on hepatic histology and Toll-like receptor 4 (TLR4) signaling pathway in mice. Methods Thirty male C57BL/6J mice were randomly divided into normal (n=10) and endotoxin (n=10) groups,fed with normal diet,and high-fat (n=10) group,fed with high-fat diet. The mice in endotoxin group were implanted with subcutaneous osmotic minipump to infuse endotoxin at 300 μg·kg-1·d-1 for 4 weeks. The mice in normal group were implanted with minipump filled with saline as control. At the end of the 4th week,the serum endotoxin level were detected. NAFLD activity score (NAS) of liver tissue was evaluated. The mRNA levels of hepatic TLR4,MyD88 and TRAM were detected by real time PCR. Results Serum endotoxin level in endotoxin group [(0.62±0.04) EU/ml] was significantly higher than that in normal group [(0.50±0.06) EU/ml,P<0.05] and in high-fat group [(0.49±0.05) EU/ml,P<0.05];The dominant histology change of liver in endotoxin mice was simple steatosis and the NAS score was (2.30 ±0.49), while the mice in high-fat group had more severe hepatic inflammation and the NAS score was(4.20±1.61),which was significantly higher than that in the endotoxin group(P<0.05);The TLR4 mRNA level in endotoxin group was 5.12 times higher (P<0.01) and TRAM mRNA level was 3.46 times higher (P<0.01) as compared with in normal group, but the MyD88 mRNA levels in the three groups had no significant difference. Conclusion Four-week mimic metabolic endotoxemia induces hepatic steatosis with increased levels of hepatic TLR4 and TRAM mRNA, but has no effect on the hepatic MyD88 mRNA.
