宫内缺氧对成年大鼠胰岛素抵抗和胰岛β细胞功能的影响

Impact of intrauterine chronic hypoxia on insulin resistance and islet β-cell function in adult male rat offspring

目的研究宫内慢性缺氧对成年大鼠胰岛素抵抗和胰岛β细胞功能的影响。方法 SD孕鼠16只随机分为对照组和宫内慢性缺氧组。观察子鼠生长发育状况,于12周龄每窝随机选取雄性子鼠各1只,采用稳态模式评估胰岛素抵抗(HOMA-IR);胰腺切片H-E染色观察胰岛形态;免疫组织化学染色及图像分析检测胰岛中胰岛素、Bcl-2、Bax、NF-κB表达。结果宫内慢性缺氧组子鼠出生时及12周龄胰腺质量/体质量比值明显低于对照组;成年大鼠HOMA-IR明显高于对照组;胰岛多数增生肥大;胰岛胰岛素的表达明显减弱;胰岛Bax、NF-κB的表达高于对照组,Bcl-2的表达差异无统计学意义。结论宫内慢性缺氧可导致子代大鼠胰腺发育受损;大鼠成年后存在胰岛素抵抗和胰岛β细胞功能障碍,后者可能与胰岛β细胞胰岛素抵抗、凋亡增加有关。

Objective To investigate the impact of intrauterine chronic hypoxia on insulin resistance and islet β-cell function in the adult male rat offspring. Methods Sixteen pregnant SD rats were divided randomly into the normal control （NC） and intrauterine chronic hypoxia （ICH） groups. The growth and development status of offspring were investigated. When the descendant rats were 12 weeks old, a male offspring from each mother rat was randomly selected. Insulin resistance was evaluated with homeostasis model of assessment for insulin resistance （HOMA-IR） index. The morphology of pancreatic islet was observed by hematoxylin staining. The expressions of insulin, Bcl-2, Bax, NF-κB in pancreatic islets were detected by immunohistochemistry. Results The pancreas-to-body weight of newborns and 12-weeks old offspring in ICH group was lower than that in NC group. HOMA-IR was higher in the ICH offspring than that in controls. The pancreatic islets in ICH adult male offspring presented hyperplasia and hypertrophy. The expression of insulin was lower, but the expression of Bax and NF-κB was significantly higher in ICH adult male offspring than those in controls. There was no significant difference in expression of Bcl-2 in islet between two groups. Conclusion Exposure to intrauterine chronic hypoxia might lead to insulin resistance and dysfunction in β-cells of offspring when they grow to adults.