本文選題：尼古丁　切入點：海馬　出處：《中國藥理學(xué)與毒理學(xué)雜志》2017年01期 　論文類型：期刊論文

【摘要】：目的觀察孕期尼古丁暴露(PNE)所致子代大鼠高脂飲食下下丘腦-垂體-腎上腺(HPA)軸應(yīng)激高敏感性改變,并探討其發(fā)生機制。方法受孕Wistar大鼠從孕9~20 d sc給予尼古丁2 mg·kg-1。自然出生仔鼠斷奶后給予高脂飲食喂養(yǎng)至20周(PW20),其中一半仔鼠從PW17至PW20給予3周不可預(yù)計性慢性刺激(UCS)。HE染色觀察組織形態(tài)學(xué)改變,放免試劑盒和ELISA分別檢測大鼠血清促腎上腺皮質(zhì)激素(ACTH)及皮質(zhì)酮(CORT)水平,PCR檢測ACTH釋放激素(CRH)、精氨酸加壓素(AVP)、囊泡谷氨酸轉(zhuǎn)運蛋白2(VGlu T2)、谷氨酸脫羧酶65(GAD65)、鹽皮質(zhì)激素受體(MR)、糖皮質(zhì)激素受體(GR)和谷氨酸脫羧酶67(GAD67)等相關(guān)基因的m RNA表達。結(jié)果正常對照組雌、雄仔大鼠經(jīng)UCS刺激后,血清ACTH和CORT分別升高了1.96倍(P0.01),1.63倍(P0.01)和3.24倍(P0.01),3.54倍(P0.01),PNE組雌、雄仔大鼠經(jīng)UCS刺激后,血清ACTH和CORT分別升高了3.96倍(P0.01),3.04倍(P0.01)和5.98倍(P0.01),5.22倍(P0.01)。與UCS處理的正常對照組仔大鼠相比,UCS處理的PNE組雌、雄仔大鼠下丘腦AVP m RNA表達分別升高了2.04倍(P0.01)和1.13倍(P0.05),雌性下丘腦CRH m RNA表達和VGlu T2/GAD65 m RNA比值分別升高了2.49倍(P0.01)和1.14倍(P0.01)。全部PNE組雌、雄仔大鼠海馬各區(qū)均出現(xiàn)不同程度的病理損傷,表現(xiàn)為神經(jīng)元數(shù)量減少、排列稀疏和細胞間隙增大。與無UCS處理的正常對照組相比,無UCS處理的PNE雌、雄仔大鼠海馬MR/GR m RNA比值分別降低了88.0%和86.0%(P0.01),GAD67 m RNA表達分別升高了1.38倍和1.97倍(P0.05);與UCS處理的正常對照組相比,UCS處理的PNE組雌性仔大鼠海馬GAD67 m RNA表達升高了2.17倍(P0.05)。結(jié)論 PNE可致高脂飲食成年子代大鼠HPA軸應(yīng)激高敏感性發(fā)生,其機制可能與海馬MR/GR比值失衡、GAD67表達上調(diào),進而介導(dǎo)下丘腦局部潛在興奮性增加有關(guān)。
[Abstract]:Objective to observe the changes of hypersensitivity of hypothalamus-pituitary-adrenal (HPA) axis stress induced by nicotine exposure in pregnant rats under high-fat diet. Methods pregnant Wistar rats were given nicotine 2 mg 路kg-1.After weaning, they were fed with high-fat diet for 20 weeks, and half of them were given unpredictable chronic 3 weeks from PW17 to PW20. The histopathological changes were observed by stimulating UCSN. He staining. Radioimmunoassay kit and ELISA were used to detect the serum levels of ACTH and Cort, respectively. ACTH releasing hormone (ACTH), arginine vasopressin (AVP), vesicular glutamate transporter 2 (VGlu T2N), glutamate decarboxylase 65 (GAD65) and salt corticosteroid were detected by PCR. The expression of m RNA in the related genes, such as receptor MRN, glucocorticoid receptor GRG and glutamate decarboxylase 67GAD67. After stimulated by UCS, the serum ACTH and CORT of male rats were increased by 1.96 times (P 0.01), 1.63 times (P 0.01) and 3.24 times (P 0.01) and 3.54 times (P 0.01) respectively. The male rats were stimulated by UCS. Serum ACTH and CORT were increased by 3.96 times (P 0.01) and 5.98 times (P 0.01) and 5.22 times (P 0.01) respectively. Compared with the control group treated with UCS, the female of PNE group treated with UCS was higher than that of control group. The expression of AVP m RNA in hypothalamus of male rats was increased by 2.04 times (P 0.01) and 1.13 times (P 0.05), and the expression of CRH m RNA and VGlu T 2 / GAD 65 m RNA in female hypothalamus were increased by 2.49 times (P 0.01) and 1.14 times (P 0.01) respectively. Pathological damage was observed in the hippocampal regions of male rats. The number of neurons was decreased, the arrangement of neurons was sparse and the intercellular space was enlarged. Compared with the normal control group without UCS treatment, the female with PNE without UCS treatment was not treated with PNE. The ratio of MR/GR m RNA in hippocampus of male rats decreased by 88.0% and 86.0, respectively, and the expression of GAD67m RNA increased by 1.38 times and 1.97 times, respectively, and the expression of GAD67 m RNA increased by 2.17 times compared with the normal control group treated with UCS. Conclusion PNE can induce high sensitivity of HPA axis stress in adult offspring of high fat diet. The mechanism may be related to the up-regulation of GAD67 expression in hippocampus due to the imbalance of MR/GR ratio, which may mediate the increase of local potential excitability in hypothalamus.
【作者單位】： 武漢大學(xué)基礎(chǔ)醫(yī)學(xué)院藥理學(xué)系;發(fā)育源性疾病湖北省重點實驗室;
【基金】：國家自然科學(xué)基金(81220108026) 國家科學(xué)自然基金(81371483);國家科學(xué)自然基金(81430089)~~
【分類號】：R114

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