慢性束缚应激致大鼠持续性高血糖症与孤束核损伤有关

毕文杰 郑翔*

doi:10.16098/j.issn.0529-1356.2019.04.004

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解剖学报 ›› 2019, Vol. 50 ›› Issue (4) : 423-430. DOI: 10.16098/j.issn.0529-1356.2019.04.004

神经生物学

慢性束缚应激致大鼠持续性高血糖症与孤束核损伤有关

毕文杰¹ 郑翔^2*

作者信息 +

Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury

BI Wen-jie¹ ZHENG Xiang^2*

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摘要

目的探讨孤束核联合亚核前部（acNTS）损伤在慢性束缚应激（CRS）所致的胰岛素抵抗性高血糖症发生中的作用。方法采用CRS大鼠模型（n=20;7 d束缚+3 d自由活动，共40 d），检测葡萄糖代谢相关指标。结果 CRS导致约1/3的个体（n=7）持续性的中度胰岛素抵抗性高血糖（空腹血糖不超过11 mmol/L）。CRS高血糖鼠acNTS可观察到神经元染色浓缩，Caspase-3表达和TUNEL阳性染色，提示出现神经元凋亡样改变。机械损伤acNTS（n=6），空腹血糖水平逐渐升高，也能导致胰岛素抵抗性高血糖, 且高胰岛素血症、胰岛平均体积增大和血清皮质酮水平不变等特点与CRS小鼠一致。结论 CRS损伤了acNTS的葡萄糖敏感神经元，从而使血糖调节紊乱。

Abstract

Objective To investigate the role of anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) injury in insulin-resistant hyperglycemia during chronic restraint stress (CRS). Methods We produced the CRS models (n=20， a 7-day restraint followed by a 3-day free moving procedure for 40 days) in rats, and detected the parameters related to glucose metabolism. Results The CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulinresistant hyperglycemia in about 1/3 (n=7) of the individuals. CRS-hyperglycemic rats showed a condensed staining of acNTS neurons, and Caspase-3 immunostaining and TUNEL also showed positive, indicating apoptotic changes of acNTS neurons. After acNTS mechanical damage (n=6), the blood glucose level rised gradually, which also led to insulin-resistant hyperglycemia. The characteristics of hyperinsulinemia, increased islet volume, and serum corticosterone levels in acNTS mice were consistent with those of CRS mice. Conclusion The result indicates that during CRS, injury (apoptosis) of glucose-sensitive acNTS neurons causes dysregulation of blood glucose. Restraint stress model has value as a potential application in the study of stress-induced hyperglycemia.

关键词

慢性束缚应激,胰岛素抵抗性高血糖,神经元损伤,孤束核,酶联免疫吸附测定 / 大鼠

Key words

Chronic restraint stress

/ Insulin-resistant hyperglycemia / Neuron injury / Nucleus tractus solitaries / Enzyme-linked immunosorbent assay / Rat

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毕文杰郑翔. 慢性束缚应激致大鼠持续性高血糖症与孤束核损伤有关[J]. 解剖学报. 2019, 50(4): 423-430 https://doi.org/10.16098/j.issn.0529-1356.2019.04.004

BI Wen-jie ZHENG Xiang. Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury[J]. Acta Anatomica Sinica. 2019, 50(4): 423-430 https://doi.org/10.16098/j.issn.0529-1356.2019.04.004

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