CAJ | 학술논문

目的通过构建慢性间歇低氧大鼠模型,检测模型大鼠空腹血糖、胰岛素水平及胰岛素抵抗指数并检测大鼠肝细胞SOCS3蛋白及其mRNA表达量的变化,探讨慢性间歇低氧对胰岛素抵抗的影响.方法选取健康雄性SD大鼠24只,按随机数字表法分为正常对照组(NC组)、慢性间歇低氧2周组(CIH2组)、慢性间歇低氧5周组(CIH5组),每组8只.NC组无间歇低氧暴露,CIH2组、CIH5组暴露于间歇低氧环境中(每日8h,舱内最低氧浓度为6％～7％).分别于第15天、第36天测定大鼠空腹血糖、放射免疫法测空腹胰岛素水平并按稳态模型评估法(HOMA)计算胰岛素抵抗指数,SABC法免疫组织化学试剂盒检测大鼠肝细胞SOCS3蛋白表达,以平均灰度值表示SOCS3蛋白表达量,荧光定量-PCR法检测SOCS3-mRNA基因表达量.结果与NC组比较,CIH2与CIH5组空腹血糖水平(差异有统计学意义,F=33.582,P＜0.05)、胰岛素水平(差异有统计学意义,F=35.633,P＜0.05)及HOMA-IR(差异有统计学意义,F=49.045,P＜0.05)升高,且CIH5组最为显著(P＜0.05);与NC组比较,CIH2与CIH5组SOCS3蛋白表达升高(差异有统计学意义,F=9.472,P＜0.05),CIH2与CIH5组差异无统计学意义(P＞0.05);与NC组及CIH2组比较,CIH5组SOCS3-mRNA表达升高(差异有统计学意义,F =8.665,P＜0.05),CIH2组升高不明显(差异无统计学意义,P＞0.05).Pearson相关分析显示HOMA-IR与SOCS3平均灰度值呈负相关(r=-0.759,P＜0.001),HOMA-IR与SOCS3-mRNA呈正相关(r=0.603,P=0.01).结论 ①CIH暴露使大鼠胰岛素水平及血糖水平升高且发生胰岛素抵抗,且随间歇低氧暴露时间延长,胰岛素抵抗程度加重.②CIH导致大鼠肝细胞内SOCS3蛋白表达增高,SOCS3-mRNA基因表达上调,CIH可能通过SOCS3参与了胰岛素抵抗的发生发展.
목적 통과구건만성간헐저양대서모형,검측모형대서공복혈당、이도소수평급이도소저항지수병검측대서간세포SOCS3단백급기mRNA표체량적변화,탐토만성간헐저양대이도소저항적영향.방법 선취건강웅성SD대서24지,안수궤수자표법분위정상대조조(NC조)、만성간헐저양2주조(CIH2조)、만성간헐저양5주조(CIH5조),매조8지.NC조무간헐저양폭로,CIH2조、CIH5조폭로우간헐저양배경중(매일8h,창내최저양농도위6％～7％).분별우제15천、제36천측정대서공복혈당、방사면역법측공복이도소수평병안은태모형평고법(HOMA)계산이도소저항지수,SABC법면역조직화학시제합검측대서간세포SOCS3단백표체,이평균회도치표시SOCS3단백표체량,형광정량-PCR법검측SOCS3-mRNA기인표체량.결과 여NC조비교,CIH2여CIH5조공복혈당수평(차이유통계학의의,F=33.582,P＜0.05)、이도소수평(차이유통계학의의,F=35.633,P＜0.05)급HOMA-IR(차이유통계학의의,F=49.045,P＜0.05)승고,차CIH5조최위현저(P＜0.05);여NC조비교,CIH2여CIH5조SOCS3단백표체승고(차이유통계학의의,F=9.472,P＜0.05),CIH2여CIH5조차이무통계학의의(P＞0.05);여NC조급CIH2조비교,CIH5조SOCS3-mRNA표체승고(차이유통계학의의,F =8.665,P＜0.05),CIH2조승고불명현(차이무통계학의의,P＞0.05).Pearson상관분석현시HOMA-IR여SOCS3평균회도치정부상관(r=-0.759,P＜0.001),HOMA-IR여SOCS3-mRNA정정상관(r=0.603,P=0.01).결론 ①CIH폭로사대서이도소수평급혈당수평승고차발생이도소저항,차수간헐저양폭로시간연장,이도소저항정도가중.②CIH도치대서간세포내SOCS3단백표체증고,SOCS3-mRNA기인표체상조,CIH가능통과SOCS3삼여료이도소저항적발생발전.
Objective To established chronic intermittent hypoxic (CIH) animal model for investigate the mechanism of insulin resistance caused by CIH.Methods Twenty-four healthy male SD rats were randomly divided into four groups:normal control group (NC group),CIH 2 weeks group (CIH2 group),and CIH 5 weeks group (CIH5 group),with 8 rats in each group.The minimum oxygen concentration was 6％-7％ in animal chamber.About 8 hours per day (from 9AM to 5 PM),the experimental lasted for 35 days.The rats in control group were placed in the same animal box without CIH.After the experiment,to measure fasting blood glucose and insulin levels by radioimmunoassay and then according to the homeostasis model of insulin resistance index (HOMA) was calculated.The expressions of SOCS3 protein were detected with immunohistochemical method in rat liver cells.To detect the SOCS3-mRNA gene expression by reverse transcription and polymerase chain reaction (RT-PCR).Results Compared with the NC group,fasting blood glucose(F =33.582,P ＜0.05),insulin level (F =35.633,P ＜0.05) and HOMA-IR (F =49.045,P ＜0.05) of the CIH2.CIH5 group was higher than other groups (P ＜0.05).Compared with the NC group,the expression of SOCS3 protein was increased in CIH2 and CHI5 group (F =9.472,P ＜0.05),but in CIH2 and CIH5 group were no significantly differences (P ＞0.05).And then the expression of SOCS3-mRNA in CIH5 was higher than CIH2 and CIH5 group (F =8.665,P ＜ 0.05).Pearson correlation analysis showed that HOMA-IR and the expression of SOCS3 protein was negatively correlated (r =-0.759,P ＜0.001) and was positively correlated with SOCS3-mRNA (r =0.603,P =0.01).Conclusions ①CIH exposure caused fasting blood glucose level and increase insulin level and insulin resistance in rats with CIH.With the intermittent hypoxic exposure time prolonged,the degree of insulin resistance was increased.②CIH leads to increased expression of SOCS3 protein and SOCS3-mRNA gene in rat liver cells with CIH exposure,SOCS3 may be involved in the development of insulin resistance.