父代糖尿病引起子代代谢紊乱的研究

发布时间：2018-03-06 14:11

本文选题：糖尿病　切入点：代谢紊乱　出处：《重庆医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的：流行病学研究表明,父亲或母亲患糖尿病是子代患糖尿病的重要危险因素。母亲患糖尿病及妊娠期合并糖尿病对子代代谢的影响已有系统和深入的研究,但父亲患糖尿病对子代生长发育及代谢的影响尚不明确。因此本课题考察了父代糖尿病所生子代的生长发育及代谢情况,旨在明确父代糖尿病对子代生长发育和代谢的影响及机制。方法：雄性SD大鼠腹腔注射链脲佐菌素(35 mg/kg),选择血糖持续高于16.7 mM低于26.0 mM的动物作为糖尿病模型,与正常雌鼠交配;子鼠出生后监测体重、随机血糖和空腹血糖；实施葡萄糖耐量、高胰岛素正常血糖钳夹实验；观测体型；监测摄食量。处死动物后,收集血清和肝脏组织。血清检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL)及低密度脂蛋白(LDL)；肝脏组织进行HE染色、油红O染色、透射电子显微镜观测、TG测定、全基因组甲基化分析。结果：父代糖尿病组大鼠血糖水平显著高于对照组。与对照组相比,糖尿病组子代体重明显增加、葡萄糖耐量受损、摄食量增加,但两组随机血糖及空腹血糖未见明显差异。血清生化指标检测显示,与对照组相比,糖尿病子代组血清ALT、AST水平并无显著变化,但TC、TG、 LDL水平升高、HDL水平降低。糖尿病组子代肝脏细胞内有大量脂质堆积、肝脏TG含量明显增多；透射电镜观察到糖尿病组子代肝脏细胞出现内质网扩张。老年期时,糖尿病子代葡萄糖耐量受损加重,胰岛素敏感性明显降低。肝脏全基因甲基化分析表明,糖尿病子代肝细胞大量基因甲基化水平发生变化。结论：父代糖尿病可导致子代代谢紊乱,患糖尿病风险升高；结果初步显示表观遗传学机制可能参与父代糖尿病致子代代谢改变。
[Abstract]:Objective: epidemiological studies have shown that maternal or father diabetes is an important risk factor of diabetes in offspring. However, the effects of diabetes mellitus on the growth and metabolism of offspring were not clear. Methods: male Sprague-Dawley rats were injected intraperitoneally with streptozotocin 35 mg 路kg ~ (-1), and animals whose blood glucose was higher than 16.7 mm < 26.0 mm were selected as diabetic model. Mating with normal female mice; monitoring body weight, random blood glucose and fasting blood glucose after birth; glucose tolerance, hyperinsulinemia, normal glucose clamp test; body type; food intake; Serum and liver tissues were collected. Serum levels of alanine aminotransferase (alt), alanine aminotransferase (alt), aspartate, total cholesterol (TC), triglyceride (TGG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were detected. Liver tissues were stained by HE and oil red O staining. Transmission electron microscope (TEM) was used to detect TG and analyze the whole genome methylation. Results: the blood glucose level of the rats in the paternal diabetes group was significantly higher than that in the control group. Compared with the control group, the body weight of the offspring of the diabetic group was significantly increased, and the glucose tolerance was impaired. There was no significant difference in the level of serum alt and AST between the two groups, but there was no significant difference between the two groups in blood glucose and fasting blood glucose. The serum biochemical indexes showed that there was no significant change in serum alt AST level in the diabetic offspring group compared with the control group, but no significant difference was found between the two groups. However, the levels of TCG and LDL increased and decreased. There was a large amount of lipids accumulated in the liver cells of the offspring of diabetic group, and the content of TG in the liver was obviously increased, and the endoplasmic reticulum dilated in the liver cells of the offspring of the diabetic group was observed by transmission electron microscope. Impaired glucose tolerance and decreased insulin sensitivity were observed in diabetic offspring. Conclusion: paternal diabetes can lead to metabolic disorder in offspring and increase the risk of diabetes. Results the epigenetic mechanism may be involved in the metabolic changes of offspring induced by paternal diabetes.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

【相似文献】