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复发性低血糖和阿片类拮抗剂对低血糖相关自主神经功能衰竭大鼠模型肾上腺儿茶酚胺合成能力的影响

The effects of recurrent hypoglycaemia and opioid antagonists on the adrenal catecholamine synthetic capacity in a rat model of HAAF.

作者信息

Senthilkumaran Manjula, Bobrovskaya Larisa

机构信息

School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia.

School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia.

出版信息

Auton Neurosci. 2018 Mar;210:76-80. doi: 10.1016/j.autneu.2017.12.004. Epub 2017 Dec 16.

DOI:10.1016/j.autneu.2017.12.004
PMID:29290404
Abstract

In this study, we investigated the effects of recurrent hypoglycaemia on the adrenal catecholamine synthetic enzymes in a rat model of hypoglycaemia-associated autonomic failure (HAAF). We found that plasma adrenaline was significantly reduced by about 50% in response to recurrent hypoglycaemia versus single hypoglycaemia. However, tyrosine hydroxylase (TH) protein and phosphorylation at Ser31 and Ser40 were increased in HAAF; similarly, aromatic aminoacid decarboxylase protein was also increased indicating a likely increase in catecholamine synthesis in the adrenal gland. Opioid antagonists, naloxone and methylnaltrexone did not restore plasma adrenaline in HAAF; however, naloxone increased TH phosphorylation at Ser31 and Ser40.

摘要

在本研究中,我们在低血糖相关自主神经功能衰竭(HAAF)大鼠模型中研究了反复低血糖对肾上腺儿茶酚胺合成酶的影响。我们发现,与单次低血糖相比,反复低血糖使血浆肾上腺素显著降低了约50%。然而,HAAF中酪氨酸羟化酶(TH)蛋白以及Ser31和Ser40位点的磷酸化增加;同样,芳香族氨基酸脱羧酶蛋白也增加,表明肾上腺中儿茶酚胺合成可能增加。阿片类拮抗剂纳洛酮和甲基纳曲酮未能恢复HAAF中的血浆肾上腺素;然而,纳洛酮增加了Ser31和Ser40位点的TH磷酸化。

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Slow but Steady-The Responsiveness of Sympathoadrenal System to a Hypoglycemic Challenge in Ketogenic Diet-Fed Rats.慢而稳定——生酮饮食喂养的大鼠对低血糖挑战的交感肾上腺系统反应性。
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Leptin treatment prevents impaired hypoglycemic counterregulation induced by exposure to severe caloric restriction or exposure to recurrent hypoglycemia.
瘦素治疗可预防因暴露于严重热量限制或反复发生低血糖而导致的低血糖时的血糖调节受损。
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