中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2015年
4期
349-353
,共5页
沈卫东%陈海姣%许庆华%张伟%刘鹏飞
瀋衛東%陳海姣%許慶華%張偉%劉鵬飛
침위동%진해교%허경화%장위%류붕비
非酒精性脂肪性肝病%缺氧诱导因子-1α%表达
非酒精性脂肪性肝病%缺氧誘導因子-1α%錶達
비주정성지방성간병%결양유도인자-1α%표체
Nonacoholic fatty liver disease%Hypoxia induced factor-1α%Expression
目的 探讨缺氧诱导因子-1α(HIF-1α)信号在不同程度非酒精性脂肪性肝病中的表达及作用.方法 选40只雄性SD大鼠按随机表法随机分为正常对照组、模型组(高脂饮食4周组、8周组、12周组及16周组),每组8只.通过高脂饲料建立大鼠脂肪肝模型,取血及肝组织,进行血脂、肝功能指标、空腹血糖及病理组织学检查,运用实时定量PCR法检测肝组织中HIF-1α、过氧化物酶体增殖物受体α(PPARα)及核转录因子-κB (NF-κB)的mRNA转录水平,多组计量资料比较采用成组设计的方差分析、Kruskal-WallisH检验,两两比较采用LSD法,P＜0.05为差异有统计学意义.结果 各模型组空腹血糖水平与对照组无显著差异,在高脂饮食第12周、16周,丙氨酸氨基转移酶、甘油三酯、总胆固醇水平较对照组显著升高(P＜0.05),而高密度脂蛋白胆固醇则显著下降(P＜0.05).在高脂饮食8周后,HIF-1α表达较对照组显著升高;在高脂饮食4周后,PPARα表达较对照组显著升高;NF-κB表达随着高脂饮食的时间延长,表达逐渐升高(P＜0.05).HIF-1α mRNA表达与PPARα具有相关性(r=0.82,P＜0.05),与NF-κB亦具有相关性(r=0.67,P＜0.05),PPARα mRNA与NF-κB具有相关性(r=0.78,P＜0.05).结论 HIF-1α信号可能通过PPARα/NF-κB途径参与非酒精性脂肪性肝病的进展.
目的 探討缺氧誘導因子-1α(HIF-1α)信號在不同程度非酒精性脂肪性肝病中的錶達及作用.方法 選40隻雄性SD大鼠按隨機錶法隨機分為正常對照組、模型組(高脂飲食4週組、8週組、12週組及16週組),每組8隻.通過高脂飼料建立大鼠脂肪肝模型,取血及肝組織,進行血脂、肝功能指標、空腹血糖及病理組織學檢查,運用實時定量PCR法檢測肝組織中HIF-1α、過氧化物酶體增殖物受體α(PPARα)及覈轉錄因子-κB (NF-κB)的mRNA轉錄水平,多組計量資料比較採用成組設計的方差分析、Kruskal-WallisH檢驗,兩兩比較採用LSD法,P＜0.05為差異有統計學意義.結果 各模型組空腹血糖水平與對照組無顯著差異,在高脂飲食第12週、16週,丙氨痠氨基轉移酶、甘油三酯、總膽固醇水平較對照組顯著升高(P＜0.05),而高密度脂蛋白膽固醇則顯著下降(P＜0.05).在高脂飲食8週後,HIF-1α錶達較對照組顯著升高;在高脂飲食4週後,PPARα錶達較對照組顯著升高;NF-κB錶達隨著高脂飲食的時間延長,錶達逐漸升高(P＜0.05).HIF-1α mRNA錶達與PPARα具有相關性(r=0.82,P＜0.05),與NF-κB亦具有相關性(r=0.67,P＜0.05),PPARα mRNA與NF-κB具有相關性(r=0.78,P＜0.05).結論 HIF-1α信號可能通過PPARα/NF-κB途徑參與非酒精性脂肪性肝病的進展.
목적 탐토결양유도인자-1α(HIF-1α)신호재불동정도비주정성지방성간병중적표체급작용.방법 선40지웅성SD대서안수궤표법수궤분위정상대조조、모형조(고지음식4주조、8주조、12주조급16주조),매조8지.통과고지사료건립대서지방간모형,취혈급간조직,진행혈지、간공능지표、공복혈당급병리조직학검사,운용실시정량PCR법검측간조직중HIF-1α、과양화물매체증식물수체α(PPARα)급핵전록인자-κB (NF-κB)적mRNA전록수평,다조계량자료비교채용성조설계적방차분석、Kruskal-WallisH검험,량량비교채용LSD법,P＜0.05위차이유통계학의의.결과 각모형조공복혈당수평여대조조무현저차이,재고지음식제12주、16주,병안산안기전이매、감유삼지、총담고순수평교대조조현저승고(P＜0.05),이고밀도지단백담고순칙현저하강(P＜0.05).재고지음식8주후,HIF-1α표체교대조조현저승고;재고지음식4주후,PPARα표체교대조조현저승고;NF-κB표체수착고지음식적시간연장,표체축점승고(P＜0.05).HIF-1α mRNA표체여PPARα구유상관성(r=0.82,P＜0.05),여NF-κB역구유상관성(r=0.67,P＜0.05),PPARα mRNA여NF-κB구유상관성(r=0.78,P＜0.05).결론 HIF-1α신호가능통과PPARα/NF-κB도경삼여비주정성지방성간병적진전.
Objective To investigate the role of hypoxia induced factor-1 α (HIF-1 α) signaling pathway in development of nonacoholic fatty liver disease (NAFLD) by using a rat model.Methods Forty SD rats were randomly divided into 5 groups (normal control group,4 weeks model group,8 weeks model group,12 weeks model group,and 16 weeks model group according to random number table).NAFLD model was induced by high fat diet.Serum biochemical parameters and liver histological examinations were observed.The HIF-1α,peroxisome proliferator-activated receptor α (PPARα),and nuclear factor-κB (NF-κB) mRNA transcriptions of liver tissue were detected with realtime PCR.Results Compared with the control group,a remarkable rise of serum alanine amiotransferase,triglyceride,cholesterol,and reduction of high density lipoprotein-cholesterol were observed in rats treated with high fat diet after 12 weeks and 16 weeks (P＜0.05).Compared with model group,steatosis,grade of inflammation,and degree of fibrosis in the liver were also significantly aggravated.Fed with high fat diet for 8 weeks,the expression of HIF-1α was significantly higher than that in the control group;the expression of PPARα in 4 weeks group was significantly higher than that in the control group.The expression of PPARα was again significantly elevated in 16 weeks group (P＜0.05);NF-κB expression was increased gradually with high fat diet (P＜0.05).The expression of HIF-1 α mRNA was related with PPARα (r =0.82,P＜0.05) and NF-κB (r =0.67,P＜0.05),and PPARα mRNA was related with NF-κB (r =0.78,P＜0.05).Conclusion HIF-1 α signaling may regulate PPARα/NF-κB and seems to be related with development of NAFLD.
