CAJ | 학술논문

目的：探讨慢性间歇低氧(CIH)对大鼠肝细胞蛋白酪氨酸磷酸酶-1B(protein tyrosine phosphatase-1B,PTP-1B)及胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)蛋白表达量的影响及其导致胰岛素抵抗发生的可能机制。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4周组(CIH4组)、慢性间歇低氧8周组(CIH8组),每组8只。NC 组无间歇低氧暴露正常饲养,CIH4组及 CIH8组于上午9时至下午5时放入间歇低氧仓暴露于间歇低氧环境中,舱内最低氧浓度为6%~7%。分别于第4周及第8周检测大鼠空腹血糖及空腹胰岛素水平,用稳态模型胰岛素抵抗指数(HOMA-IR)以及胰岛素敏感指数(insulin sensitive index,ISI)评价胰岛素抵抗, SABC 法免疫组织化学试剂盒检测 CIH 大鼠肝细胞 PTP-1B 及 IRS-1蛋白表达,以平均灰度值表示PTP-1B 及 IRS-1的蛋白表达量,并做统计学分析。结果与 NC 组比较,CIH4组及 CIH8组空腹血糖、空腹胰岛素及 HOMA-IR 升高,ISI 降低,差异有统计学意义(P <0.05),且 CIH8组更为显著；与 NC 组相比较,CIH4组及 CIH8组 PTP-1B 蛋白表达增加,IRS-1蛋白表达减少,差异有统计学意义(P <0.05),Pearson 相关分析显示,HOMA-IR 与 PTP-1B 平均灰度值呈负相关、与 IRS-1平均灰度值呈正相关；ISI 与 PTP-1B 平均灰度值呈正相关、与 IRS-1平均灰度值呈负相关。结论①CIH 暴露使大鼠空腹血糖及胰岛素水平升高且发生胰岛素抵抗,随着 CIH 暴露时间的延长,胰岛素抵抗程度加重。②CIH 导致大鼠肝细胞 PTP-1B 蛋白表达增加,IRS-1蛋白表达减少,PTP-1B 及 IRS-1可能共同参与了 CIH 大鼠胰岛素抵抗的发生发展。
목적：탐토만성간헐저양(CIH)대대서간세포단백락안산린산매-1B(protein tyrosine phosphatase-1B,PTP-1B)급이도소수체저물-1(insulin receptor substrate-1,IRS-1)단백표체량적영향급기도치이도소저항발생적가능궤제。방법선취건강웅성 SD 대서24지,안수궤수자표법분위정상대조조(NC 조)、만성간헐저양4주조(CIH4조)、만성간헐저양8주조(CIH8조),매조8지。NC 조무간헐저양폭로정상사양,CIH4조급 CIH8조우상오9시지하오5시방입간헐저양창폭로우간헐저양배경중,창내최저양농도위6%~7%。분별우제4주급제8주검측대서공복혈당급공복이도소수평,용은태모형이도소저항지수(HOMA-IR)이급이도소민감지수(insulin sensitive index,ISI)평개이도소저항, SABC 법면역조직화학시제합검측 CIH 대서간세포 PTP-1B 급 IRS-1단백표체,이평균회도치표시PTP-1B 급 IRS-1적단백표체량,병주통계학분석。결과여 NC 조비교,CIH4조급 CIH8조공복혈당、공복이도소급 HOMA-IR 승고,ISI 강저,차이유통계학의의(P <0.05),차 CIH8조경위현저；여 NC 조상비교,CIH4조급 CIH8조 PTP-1B 단백표체증가,IRS-1단백표체감소,차이유통계학의의(P <0.05),Pearson 상관분석현시,HOMA-IR 여 PTP-1B 평균회도치정부상관、여 IRS-1평균회도치정정상관；ISI 여 PTP-1B 평균회도치정정상관、여 IRS-1평균회도치정부상관。결론①CIH 폭로사대서공복혈당급이도소수평승고차발생이도소저항,수착 CIH 폭로시간적연장,이도소저항정도가중。②CIH 도치대서간세포 PTP-1B 단백표체증가,IRS-1단백표체감소,PTP-1B 급 IRS-1가능공동삼여료 CIH 대서이도소저항적발생발전。
Objective To investigate the effects of chronic intermittent hypoxia on the expression of PTP-1B and IRS-1 and the possible mechanism of insulin resistance caused by chronic intermittent hypoxia.Methods According to the principle of random number,twenty-four healthy male SD rats were divided into the normal group (NC group),the four-week chronically intermittent hypoxia group (CIH4 group)and the eight-week chronically intermittent hypoxia group (CIH8 group)equally.The NC group were raised normally,while the CIH4 and the CIH8 ones were exposed to the intermittent hypoxia cabins from 9 am to 5 pm,in which the lowest air concentration was 6%- 7%.The fast blood glucose (FBG) and fasting insulin (FINS)were detected at the fourth week and the eighth week to evaluate the insulin insistence with homeostasis model assessment-insulin resistance index (HMOA-IR)and insulin sensitive index (ISI),and the average gray value indicating the expression of PTP-1B and IRS-1 protein was tested with SABC immunohistochemical kits,of which the data were analysed statistically.Results Compared to the NC group,FBG,insulin level and HOMA-IR of the CIH4,CIH8 group increased while ISI decreased (P <0.05),and the trend is more obvious in CIH8 group.Compared to the NC group,PTP-1B protein rised and IRS-1 protein declined in the expression of the CIH4 and CIH8 group (P < 0.05 ).Pearson correlation analysis showed that HOMA-IR was negatively correlated with the gray value of PTP-1B and positively corrected with that of IRS-1,ISI had a positive relationship with PTP-1IR and a negative relationship with that of IRS-1.Conclusions ①The exposure of chronically intermittent hypoxia caused increased FNG,insulin level and insulin resistence,which exacerbated as the exposure time extended.②The chronically intermittent hypoxia induced high expression of PTP-1B protein and low expression of IRS-1 in rats′ liver cells.PTP-1B and IRS might participate in the insulin resistence of rats caused by chronically intermittent hypoxia.