孕期咖啡因暴露导致子代成年雌性大鼠代谢综合征易感及发生机制

发布时间：2018-05-25 14:07

本文选题：咖啡因 + 下丘脑-垂体-肾上腺轴　；参考：《中国药理学与毒理学杂志》2017年04期

【摘要】：目的观察经历出生后早期追赶性生长和后期慢性应激的孕期咖啡因暴露(PCE)子代成年雌性大鼠代谢综合征(MS)的易感现象并探讨其发生机制。方法 Wistar大鼠于孕11 d每天ig给予咖啡因120 mg·kg~(-1)至分娩,子代雌性大鼠4周龄(PW4)~PW24给予高脂饮食,并于PW38~PW40给予2周不可预知性慢性应激,分别检测血糖及血清促肾上腺皮质激素释放激素、皮质酮、胰岛素、甘油三酯、总胆固醇、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)水平。实时定量PCR技术检测肾上腺组织的甾体合成急性调节蛋白、P450侧链裂解酶、3β-羟类固醇脱氢酶、类固醇11β-羟化酶和类固醇21β-羟化酶,以及肝组织的胰岛素受体、胰岛素受体底物2和葡萄糖转运体2(GLUT2)m RNA表达。HE染色观察肾上腺、胰腺和肝组织形态。结果 PCE子代雌性大鼠PW1时体质量为(10.5±1.0)g,显著低于对照组(13.9±2.8)g(P0.01),这种低体质量持续至PW40(P0.05,P0.01),但体质量增长率在PW4~PW16处于高水平(P0.05,P0.01)。同时,血糖〔(5.9±0.3)mmol·L~(-1)〕水平和血清胰岛素水平〔(100±31)m U·L~(-1)〕、胰岛素抵抗指数(26.3±5.7)和血清LDL-C水平〔(0.55±0.05)mmol·L~(-1)〕及LDL-C/HDL-C比值(0.87±0.11)分别高于对照组〔血糖:(4.3±0.3)mmol·L~(-1);血胰岛素:(45±4)m U·L~(-1);胰岛素抵抗指数:8.3±0.9;LDL-C:(0.38±0.04)mmol·L~(-1);LDL-C/HDL-C比值∶0.66±0.07〕(P0.05,P0.01)。PCE组肝组织GLUT2 m RNA表达低于对照组(P0.05)。光镜下可见,PCE组肾上腺束状带变薄,胰腺胰岛面积变小,而肝组织形态无明显变化。结论 PCE子代成年雌性大鼠MS易感性增加,主要表现为以高血糖和高胰岛素血症为特征的胰岛素抵抗、脂代谢紊乱、多脏器结构及功能异常,其发生与下丘脑-垂体-肾上腺轴相关的宫内神经内分泌代谢编程紊乱有关。
[Abstract]:Objective To observe the susceptibility to metabolic syndrome (MS) of adult female rats exposed to caffeine exposure (PCE) during early postnatal and late postnatal stress and to explore the mechanism of its pathogenesis. Methods Wistar rats were given caffeine 120 mg kg~ (-1) to childbirth at Ig 11 d per day, and 4 weeks old female rats (PW4) ~PW24 were given in the female rats. High fat diet and 2 weeks of unpredictable chronic stress were given at PW38~PW40. Blood glucose and serum adrenocorticotropin releasing hormone, corticosterone, insulin, triglyceride, total cholesterol, low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were measured respectively. Real-time quantitative PCR technique was used to detect the steroid synthesis of adrenal tissue. Regulating protein, P450 side chain lyase, 3 beta hydroxylsteroid dehydrogenase, steroid 11 beta hydroxylase and steroid 21 beta hydroxylase, insulin receptor of liver tissue, insulin receptor substrate 2 and glucose transporter 2 (GLUT2) m RNA expression.HE staining to observe the morphology of adrenal, pancreas and liver tissue. Results the mass of PW1 in female PCE offspring rats (10.5 + 1) g, significantly lower than the control group (13.9 + 2.8) g (P0.01), this low body mass continued to PW40 (P0.05, P0.01), but the body mass growth rate was at a high level in PW4~PW16 (P0.05, P0.01). Meanwhile, blood glucose [(5.9 + 0.3) mmol L~ (-1)] level and serum insulin level [100 + 31)], insulin resistance index (26.3 + 5.7) and blood The level of LDL-C (0.55 + 0.05) mmol / L~ (-1) and LDL-C/HDL-C (0.87 + 0.11) was higher than that of the control group [(4.3 + 0.3) mmol. L~ (-1), blood insulin: (45 + 4) m U. L~ (-1), insulin resistance index: 8.3 + 0.9, 0.38 + 0.04 The expression was lower than that of the control group (P0.05). The light microscope showed that the adrenal fascicular zone in the PCE group became thinner, the pancreas islet area became smaller, and the liver tissue morphology was not changed. Conclusion the susceptibility to MS in the adult female rats of the PCE progeny was increased, mainly characterized by hyperglycemia and hyperinsulinemia, the disorder of lipid metabolism, and the structure of multiple organs and the structure of multiple organs. Dysfunction occurs in relation to hypothalamic pituitary adrenal axis related disorders of intrauterine neuroendocrine metabolism.
【作者单位】：武汉大学基础医学院药理学系;南阳医学高等专科学校基础医学部;发育源性疾病湖北省重点实验室;
【基金】：国家自然科学基金(81220108026);国家自然科学基金(81430089)~~
【分类号】：R114

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