不同剂量果糖摄入对孕期大鼠糖代谢影响的研究

发布时间：2018-10-14 12:11

【摘要】：目的:给予孕期大鼠不同剂量果糖灌胃,观察孕期大鼠血糖、胰岛素水平及胚胎发育情况,比较不同剂量果糖摄入对孕期大鼠糖代谢的影响,初步探讨高果糖摄入致孕期大鼠糖代谢异常的机制。方法:成年雌性与雄性SD大鼠适应性喂养1周,以2:1比例合笼交配,次日晨做阴道涂片,显微镜下检查发现精子者记孕第0天,将48只孕鼠随机分为4组,即空白对照组(BC)、正常剂量果糖组(NF)、高剂量果糖组(HF)、超高剂量果糖组(SHF),分别给蒸馏水、2.0g/kg、5.0g/kg和8.0g/kg果糖各1ml灌胃,于妊娠第18天行口服葡萄糖耐量试验(OGTT),孕第20天处死。1)每日记录摄食量,每周称量体重并比较各组进食量及体重增长情况;2)孕第18天行OGTT检查,评估糖耐量;3)检测空腹胰岛素水平,计算胰岛素敏感指数和胰岛素抵抗指数,评估胰岛功能;4)留取胰腺组织苏木精-伊红染色法观察其组织形态学的变化;5)剖腹取胎鼠,观察其一般状况,比较各组胎鼠体重、着床数、死胎及吸收胎的差异。6)分离血清检测总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白水平;7)留取孕鼠肝脏组织观察称重,苏木精-伊红染色法观察其组织形态学的变化;8)酶联免疫吸附法检测炎性因子:肿瘤坏死因-α(TNF-α)、白介素-6(IL-6)的水平。结果:1)NF组、HF组和SHF组大鼠体重增加在喂养的第3周时明显高于BC组,差异有统计学意义(P0.05);2)孕第18天OGTT结果显示与BC组相比,HF组服糖15min后血糖吸收的峰值出现且明显高于BC组和NF组(P0.05),SHF组服糖30min后出现峰值,较其它各组明显延迟(P0.05);3)孕第20天,高剂量和超高剂量果糖孕鼠胰岛素水平升高、胰岛素敏感指数(ISI)及胰岛素抵抗指数(HOMA-IR)降低,差异显著(P0.05)。胰腺组织病理切片示HF组和SHF组胰岛β细胞出现不同程度的肥大、增生。4)孕期结束,HF组死胎比例分别为9.1%,明显高于BC组,SHF组吸收胎、死胎比例分别为10.0%和21.81%,明显高于BC组且SHF组胎鼠体重明显低于BC组(P0.05)。5)各果糖干预组血脂水平出现不同水平的升高,与BC组相比,HF和SHF组TC、TG水平明显升高,SHF组LDL水平明显升高,差异有统计学意义(P0.05)。肝脏病理切片观察显示,HF、SHF组有大小不等的脂质空泡,出现轻度的脂肪沉积。6)HF和SHF组血清TNF-α和IL-6水平显著升高(P0.05)。结论:1)孕期高剂量和超高剂量的果糖摄入可导致葡萄糖耐量受损和胰岛素抵抗发生。2)孕期高剂量和超高剂量的果糖摄入可致不良妊娠结局。3)高剂量和超高剂量果糖摄入致孕期糖代谢异常与果糖摄入引起的炎症因子水平升高有关。
[Abstract]:Objective: to observe the effect of fructose intake on glucose metabolism in pregnant rats by intragastric administration of fructose in different doses, and to observe the levels of blood glucose, insulin and embryonic development in pregnant rats, and to compare the effects of fructose intake with different doses on glucose metabolism in pregnant rats. To explore the mechanism of abnormal glucose metabolism in pregnant rats induced by high fructose intake. Methods: adult female and male SD rats were fed adaptively for one week, mating at 2:1. Vaginal smears were taken in the next morning. Under microscope, 48 pregnant rats were randomly divided into 4 groups. In the blank control group, (BC), normal dose fructose group, (NF), high dose fructose group, (HF), ultrahigh dose fructose group (SHF), were given distilled water, 2.0 g / kg + 5.0 g / kg and 8.0g/kg fructose 1ml, respectively. On the 18th day of pregnancy, oral glucose tolerance test (OGTT),) was performed on the 20th day of gestation. 1) daily food intake was recorded, weight was weighed weekly, and food intake and weight gain were compared. 2) OGTT examination was performed on the 18th day of pregnancy. To assess glucose tolerance; 3) to measure fasting insulin levels, calculate insulin sensitivity index and insulin resistance index, and evaluate islet function; 4) to observe histomorphologic changes of pancreatic tissue by hematoxylin-eosin staining; 5) to take fetal mice by laparotomy. Observe its general condition, compare the difference of body weight, implantation number, dead fetus and absorbent fetus in each group. 6) detect total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein in serum. 7) observe the weight of liver tissue of pregnant rats. The histomorphologic changes were observed by hematoxylin-eosin staining, and the levels of inflammatory cytokines, tumor necrosis factor- 伪 (TNF- 伪) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (Elisa). Results: 1) the weight gain of NF group, HF group and SHF group was significantly higher than that of BC group at the 3rd week of feeding. The results of OGTT on the 18th day of gestation showed that the peak value of glucose absorption in HF group was significantly higher than that in BC group and NF group (P0.05) on the 18th day of pregnancy compared with that in BC group (P0.05), which was significantly delayed than that in other groups (P0.05); (3) the peak value of glucose absorption in HF group was higher than that in BC group and NF group (P0.05). The insulin level increased and the insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) decreased in high dose and high dose fructose pregnant rats (P0.05). Pancreatic histopathological sections showed that islet 尾 cells were hypertrophy in different degrees in HF group and SHF group. 4) at the end of pregnancy, the proportion of dead fetus in HF group was 9.1 significantly higher than that in BC group, and that in SHF group was higher than that in BC group. The proportion of dead fetus was 10.0% and 21.81%, respectively, which was significantly higher than that in BC group, and the body weight of fetal rats in SHF group was significantly lower than that in BC group (P0.05). Compared with BC group, TC,TG level in HF and SHF group was significantly higher, LDL level in SHF group was significantly higher than that in BC group (P0.05). The difference was statistically significant (P0.05). Liver pathological examination showed that there were lipid vacuoles with slight fat deposition in HF,SHF group and serum TNF- 伪 and IL-6 levels in SHF group were significantly higher than those in HF group (P0.05). Conclusion: 1) High-dose and ultra-high fructose intake during pregnancy can lead to impaired glucose tolerance and insulin resistance. 2) High-dose and ultra-high fructose intake during pregnancy can result in adverse pregnancy outcome. Abnormal glucose metabolism during pregnancy induced by glucose intake was associated with increased levels of inflammatory factors induced by fructose intake.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R153.1

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