国际内分泌代谢杂志
國際內分泌代謝雜誌
국제내분비대사잡지
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2015年
1期
1-5
,共5页
慢性间歇低氧%IRS-2%FoxO1%胰岛素抵抗
慢性間歇低氧%IRS-2%FoxO1%胰島素牴抗
만성간헐저양%IRS-2%FoxO1%이도소저항
Chronic intermittent hypoxia%IRS-2%FoxO1%Insulin resistance
目的 观察慢性间歇低氧条件下,大鼠肝细胞形态学变化及胰岛素受体底物-2 (IRS-2)、叉头框蛋白O1(FoxO1)的蛋白表达,并探讨IRS-2、FoxO1与胰岛素抵抗的相关性.方法 取24只6周龄健康雄性Sprauge-Dawley大鼠,采用随机数字表法分为正常对照组(NC组)、慢性间歇低氧4周组(CIH4组)、慢性间歇低氧8周组(CIH8组),每组8只.CIH4组和CIH8组暴露于间歇低氧舱内:最低氧浓度6％ ～ 8％,持续时间8 h/d.NC组无间歇低氧暴露正常饲养,CIH4组、CIH8组和NC组分别于第4周、第8周及第8周禁食12 h后测定空腹血糖、空腹胰岛素水平,并采用稳态模型评估-胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI)评价胰岛素抵抗,对肝组织行HE染色观察形态学变化,采用免疫组织化学方法测定肝细胞IRS-2、FoxO1蛋白表达,以平均灰度值表示其蛋白表达量,二者成反比关系.结果 与NC组相比,CIH4组、CIH8组空腹血糖、胰岛素、HOMA-IR升高,ISI降低,且CIH8组更为显著,差异有统计学意义(F=50.23 ～90.26,P均＜0.05).与NC组相比,CIH4组与CIH8组IRS-2蛋白表达降低,FoxO1蛋白表达增高且在核内重新分布,CIH8组更为显著,差异有统计学意义(F=69.46,618.94,P均＜0.05).Pearson相关分析显示:HMOA-IR与IRS-2平均灰度值呈正相关(r=0.857,P＜0.05),与FoxO1平均灰度值呈负相关(r=-0.926,P＜0.05),ISI与IRS-2平均灰度值呈负相关(r=-0.823,P＜0.05),与FoxO1平均灰度值呈正相关(r=0.848,P＜0.05).结论 慢性间歇低氧条件下,大鼠肝细胞受损并发生胰岛素抵抗,同时IRS-2和FoxO1蛋白表达异常,且随暴露时间延长肝细胞损伤程度及胰岛素抵抗程度均逐渐加重.
目的 觀察慢性間歇低氧條件下,大鼠肝細胞形態學變化及胰島素受體底物-2 (IRS-2)、扠頭框蛋白O1(FoxO1)的蛋白錶達,併探討IRS-2、FoxO1與胰島素牴抗的相關性.方法 取24隻6週齡健康雄性Sprauge-Dawley大鼠,採用隨機數字錶法分為正常對照組(NC組)、慢性間歇低氧4週組(CIH4組)、慢性間歇低氧8週組(CIH8組),每組8隻.CIH4組和CIH8組暴露于間歇低氧艙內:最低氧濃度6％ ～ 8％,持續時間8 h/d.NC組無間歇低氧暴露正常飼養,CIH4組、CIH8組和NC組分彆于第4週、第8週及第8週禁食12 h後測定空腹血糖、空腹胰島素水平,併採用穩態模型評估-胰島素牴抗指數(HOMA-IR)和胰島素敏感性指數(ISI)評價胰島素牴抗,對肝組織行HE染色觀察形態學變化,採用免疫組織化學方法測定肝細胞IRS-2、FoxO1蛋白錶達,以平均灰度值錶示其蛋白錶達量,二者成反比關繫.結果 與NC組相比,CIH4組、CIH8組空腹血糖、胰島素、HOMA-IR升高,ISI降低,且CIH8組更為顯著,差異有統計學意義(F=50.23 ～90.26,P均＜0.05).與NC組相比,CIH4組與CIH8組IRS-2蛋白錶達降低,FoxO1蛋白錶達增高且在覈內重新分佈,CIH8組更為顯著,差異有統計學意義(F=69.46,618.94,P均＜0.05).Pearson相關分析顯示:HMOA-IR與IRS-2平均灰度值呈正相關(r=0.857,P＜0.05),與FoxO1平均灰度值呈負相關(r=-0.926,P＜0.05),ISI與IRS-2平均灰度值呈負相關(r=-0.823,P＜0.05),與FoxO1平均灰度值呈正相關(r=0.848,P＜0.05).結論 慢性間歇低氧條件下,大鼠肝細胞受損併髮生胰島素牴抗,同時IRS-2和FoxO1蛋白錶達異常,且隨暴露時間延長肝細胞損傷程度及胰島素牴抗程度均逐漸加重.
목적 관찰만성간헐저양조건하,대서간세포형태학변화급이도소수체저물-2 (IRS-2)、차두광단백O1(FoxO1)적단백표체,병탐토IRS-2、FoxO1여이도소저항적상관성.방법 취24지6주령건강웅성Sprauge-Dawley대서,채용수궤수자표법분위정상대조조(NC조)、만성간헐저양4주조(CIH4조)、만성간헐저양8주조(CIH8조),매조8지.CIH4조화CIH8조폭로우간헐저양창내:최저양농도6％ ～ 8％,지속시간8 h/d.NC조무간헐저양폭로정상사양,CIH4조、CIH8조화NC조분별우제4주、제8주급제8주금식12 h후측정공복혈당、공복이도소수평,병채용은태모형평고-이도소저항지수(HOMA-IR)화이도소민감성지수(ISI)평개이도소저항,대간조직행HE염색관찰형태학변화,채용면역조직화학방법측정간세포IRS-2、FoxO1단백표체,이평균회도치표시기단백표체량,이자성반비관계.결과 여NC조상비,CIH4조、CIH8조공복혈당、이도소、HOMA-IR승고,ISI강저,차CIH8조경위현저,차이유통계학의의(F=50.23 ～90.26,P균＜0.05).여NC조상비,CIH4조여CIH8조IRS-2단백표체강저,FoxO1단백표체증고차재핵내중신분포,CIH8조경위현저,차이유통계학의의(F=69.46,618.94,P균＜0.05).Pearson상관분석현시:HMOA-IR여IRS-2평균회도치정정상관(r=0.857,P＜0.05),여FoxO1평균회도치정부상관(r=-0.926,P＜0.05),ISI여IRS-2평균회도치정부상관(r=-0.823,P＜0.05),여FoxO1평균회도치정정상관(r=0.848,P＜0.05).결론 만성간헐저양조건하,대서간세포수손병발생이도소저항,동시IRS-2화FoxO1단백표체이상,차수폭로시간연장간세포손상정도급이도소저항정도균축점가중.
Objective To observe the histomorphologic alteration and expression of insulin receptor substrate (IRS)-2 and FoxO1 in rat heptocytes,and investigate the association of IRS-2 and FoxO1 with insulin resistance induced by chronic intermitted hypoxia.Methods Twenty-four healthy male Sprauge-Dawley rats at 6-week age were divided into normal control group (NC group),chronic intermittent hypoxia for 4 weeks group (CIH4 group) and chronic intermittent hypoxia for 8 weeks group (CIH8 group) according to random number table,with 8 rats in each group.CIH4 group and CIH8 group were placed in intermittent low oxygen cabin for 8 hours per day,the minimum oxygen concentration was 6％-8％.NC group was placed in normal air cabin.Fasting blood glucose and fasting insulin level were measured on 4th week,8th week and after an overnight fast of 12 hours on 8th week in CIH4,CIH8 and NC group,respectively.Homeostatic model assessment of insulin resistance index (HOMA-IR) and insulin sensitive index (ISI) were used to evaluate insulin resistance.HE staining was used for morphologic study of liver.IRS-2 and FoxO1 expression in heptocytes were analyzed by immunohistochemistry.Average gray value was used to represent the protein expression,and which was inversely proportional to average gray value.Results Compared with NC group,CIH4 and CIH8 group had elevated fasting blood glucose,fasting insulin,HOMA-IR,and reduced ISI,especially in CIH8 group (F =50.23-90.26,all P ＜ 0.05).Compared with NC group,the expression of IRS-2 decreased in CIH4 and CIH8 group;the expression of FoxO1 increased in CIH4 and CIH8 group with the re-distribution in the nucleus,especially in CIH8 group (F =69.46,618.94,all P ＜ 0.05).Pearson correlation analysis showed that HOMA-IR was positively correlated with the average gray value of IRS-2 (r =0.857,P ＜ 0.05),but was negatively correlated with the average gray value of FoxO1 (r =-0.926,P ＜ 0.05).ISI was negatively correlated with the average gray value of IRS-2 (r =-0.823,P ＜ 0.05) and was positively correlated with the average gray value of FoxO1 (r=0.848,P＜0.05).Conclusions In intermittent hypoxia,the liver is damaged along with the occurrence of insulin resistance and the abnormal expression of IRS-2 and FoxO1,which are aggravated with the exposure time of hypoxia.
