慢性间歇低氧大鼠肝细胞IRS-2与FoxO1表达水平对胰岛素抵抗的影响

发布时间：2018-04-18 01:16

本文选题：慢性间歇低氧 + IRS-2　；参考：《山西医科大学》2015年硕士论文

【摘要】：目的:通过观察慢性间歇低氧大鼠肝细胞形态学变化及肝细胞中胰岛素受体底物-2(IRS-2)、叉头框蛋白O1(Fox O1)的蛋白表达,探讨IRS-2、Fox O1可能参与慢性间歇低氧所致的胰岛素抵抗。方法:取24只6周龄健康雄性Sprauge-Dawley(SD)大鼠,采取随机数字表法将大鼠分为正常对照(NC)组、慢性间歇低氧4周(CIH4)组、慢性间歇低氧8周(CIH8)组,每组8只。CIH4组和CIH8组均暴露于间歇低氧环境内:最低氧浓度6%~8%,持续时间8 h/d。NC组给予压缩空气,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后测量大鼠空腹血糖及空腹胰岛素水平,并通过稳态模型评估-胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI)来评价胰岛素抵抗程度,对大鼠肝脏组织行HE染色观察肝脏组织形态学变化,采用免疫组织化学方法测定大鼠肝细胞IRS-2、Fox O1蛋白表达,以平均灰度值表示其蛋白表达量,二者呈反比关系,并进行统计学分析。结果:与NC组相比,CIH4组、CIH8组空腹血糖、空腹胰岛素、HOMA-IR水平升高,ISI降低,且CIH8组更为显著,差异有统计学意义(P均0.05)。与NC组相比,CIH4组与CIH8组IRS-2蛋白表达降低,Fox O1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(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,P0.05),与Fox O1平均灰度值呈负相关(r=-0.926,P0.05),ISI与IRS-2平均灰度值呈负相关(r=-0.823,P0.05),与Fox O1平均灰度值呈正相关(r=0.848,P0.05)。结论:1.慢性间歇低氧可导致大鼠肝细胞受损,且随暴露时间延长肝细胞损伤程度加重;2.慢性间歇低氧条件下,大鼠可发生胰岛素抵抗,随暴露时间延长胰岛素抵抗程度加重;3.慢性间歇低氧大鼠肝细胞IRS-2蛋白表达降低、Fox O1蛋白表达增高,且与胰岛素抵抗程度存在相关性,表明这两种蛋白可能参与慢性间歇低氧所致的胰岛素抵抗。
[Abstract]:Aim: to investigate the role of IRS-2 and Fox O1 in insulin resistance induced by chronic intermittent hypoxia by observing the morphologic changes of hepatocytes and the expression of insulin receptor substrate--2OS-2IRS-2protein (O1(Fox O1) in the hepatocytes of chronic intermittent hypoxia rats.Methods: Twenty-four 6-week-old male Sprauge-Dawley SD rats were randomly divided into normal control group (NC4), chronic intermittent hypoxia group (4-week CIH4) and chronic intermittent hypoxia group (8-week CIH8).Eight rats in each group were exposed to intermittent hypoxia: the lowest oxygen concentration was 6 / 8, the duration was 8 h/d.NC, compressed air was given to each group, and the normal feeding group was fed with compressed air for 4 weeks, respectively.Fasting fasting blood glucose and fasting insulin levels were measured in rats at 8 and 8 weeks after fasting for 12 hours, and insulin resistance was evaluated by homeostasis model evaluation-HOMA-IRI and ISI.The morphological changes of rat liver tissue were observed by HE staining. The expression of IRS-2 and Fox O1 protein in rat hepatocytes was determined by immunohistochemical method. The expression of IRS-2 Fox O1 protein was expressed by the mean gray value, which was inversely proportional to each other.Statistical analysis was carried out.Results: compared with the NC group, the fasting blood glucose and fasting insulin HOMA-IR level in the CIH4 group were higher than those in the NC group, and the level of HOMA-IR in the CIH8 group was significantly lower than that in the control group (P < 0.05).Compared with the NC group, the expression of IRS-2 protein in the CIH8 group and the control group was significantly lower than that in the control group, and the expression of IRS-2 O1 protein was significantly increased in the nuclear redistribution group.There was a positive correlation between the average gray value of IRS-2 and IRS-2, a negative correlation with the average gray value of Fox O _ 1, a negative correlation between IRS-2 and the average gray value of IRS-2, and a positive correlation between the average gray value of Fox O _ 1 and the average gray value of Fox O _ 1.Conclusion 1.Chronic intermittent hypoxia caused hepatocyte damage in rats, and the degree of hepatocyte damage was aggravated with the prolongation of exposure time.Chronic intermittent hypoxia induced insulin resistance in rats and increased insulin resistance with the prolongation of exposure time.The expression of IRS-2 protein decreased in chronic intermittent hypoxia rats and was correlated with the degree of insulin resistance, suggesting that these two proteins may be involved in insulin resistance induced by chronic intermittent hypoxia.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R766

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