Diabetes-Related Induction of the Heme Oxygenase System and Enhanced Colocalization of Heme Oxygenase 1 and 2 with Neuronal Nitric Oxide Synthase in Myenteric Neurons of Different Intestinal Segments.

Diabetes-Related Induction of the Heme Oxygenase System and Enhanced Colocalization of Heme Oxygenase 1 and 2 with Neuronal Nitric Oxide Synthase in Myenteric Neurons of Different Intestinal Segments.
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糖尿病相关的血红素加氧酶系统诱导以及不同肠段肌间神经元中血红素加氧酶 1 和 2 与神经元一氧化氮合酶的共定位增强。

DOI:
10.1155/2017/1890512
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发表时间:
2017
影响因子:
--
通讯作者:
Bódi N
Bódi N
中科院分区:
生物学2区
文献类型:
--
作者:
Chandrakumar L;Bagyánszki M;Szalai Z;Mezei D;Bódi N

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高血糖诱导的氧化应激增加和内源性防御机制的有效性下降在糖尿病相关神经病变的发生中起重要作用。我们证明了不同肠段的氮能肌群神经元对糖尿病损伤表现出不同的易感性。因此,我们的目的是揭示血红素加氧酶(HO)异构体在肠段特异性表达的差异,以及这些抗氧化剂在肌肠神经元中与神经元一氧化氮合酶(nNOS)的共定位。10周后,对对照组和链脲佐菌素诱导的糖尿病大鼠的十二指肠、回肠和结肠进行双标记荧光免疫组化和ELISA检测。对照组的回肠肌肌神经元中ho -免疫反应和nNOS/ ho -免疫反应神经元数量最少,结肠神经节中最多;它在回肠中增加最多,在糖尿病患者的结肠中也有升高。虽然在各节段氮能神经元总数减少,但在糖尿病患者的回肠和结肠中,与HOs共定位的nnos免疫反应神经元的比例明显增加。我们推测,不与HOs共定位的氮能神经元受糖尿病损伤的影响最为严重。因此,HO系统的区域诱导与糖尿病相关的区域特异性氮能性神经病密切相关。
Increase in hyperglycaemia-induced oxidative stress and decreased effectiveness of endogenous defense mechanisms plays an essential role in the initiation of diabetes-related neuropathy. We demonstrated that nitrergic myenteric neurons display different susceptibilities to diabetic damage in different gut segments. Therefore, we aim to reveal the gut segment-specific differences in the expression of heme oxygenase (HO) isoforms and the colocalization of these antioxidants with neuronal nitric oxide synthase (nNOS) in myenteric neurons. After ten weeks, samples from the duodenum, ileum, and colon of control and streptozotocin-induced diabetic rats were processed for double-labelling fluorescent immunohistochemistry and ELISA. The number of both HO-immunoreactive and nNOS/HO-immunoreactive myenteric neurons was the lowest in the ileal and the highest in the colonic ganglia of controls; it increased the most extensively in the ileum and was also elevated in the colon of diabetics. Although the total number of nitrergic neurons decreased in all segments, the proportion of nNOS-immunoreactive neurons colocalizing with HOs was enhanced robustly in the ileum and colon of diabetics. We presume that those nitrergic neurons which do not colocalize with HOs are the most seriously affected by diabetic damage. Therefore, the regional induction of the HO system is strongly correlated with diabetes-related region-specific nitrergic neuropathy.
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