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联合无机硝酸盐与一氧化氮合酶抑制剂对链脲佐菌素诱导的糖尿病大鼠胰腺氧化应激及胰岛素分泌受损的改善作用

Improving effect of combined inorganic nitrate and nitric oxide synthase inhibitor on pancreatic oxidative stress and impaired insulin secretion in streptozotocin induced-diabetic rats.

作者信息

Shahraki Zahra Shabgard, Karbalaei Narges, Nemati Marzieh

机构信息

Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

J Diabetes Metab Disord. 2020 Mar 18;19(1):353-362. doi: 10.1007/s40200-020-00516-1. eCollection 2020 Jun.

DOI:10.1007/s40200-020-00516-1
PMID:32550186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7270212/
Abstract

PURPOSE

The aim of this study was to evaluate the effect of dietary nitrate on secretory function of pancreatic islet and oxidative stress status in streptozotocin (STZ) induced type 1 diabetes in absence or presence of nitric oxide synthase inhibitor (L-NAME).

METHODS

Fifty adult male sprague-dawly rats were divided into 5 groups: controls (C), diabetes (D), diabetes+nitrate (DN), diabetes +L-NAME (D + Ln), and diabetes+nitrate+L-NAME (DN + Ln) for 45 days. The concentrations of sodium nitrate and L-NAME were respectively 80 mg/L in drinking water and 5 mg/kg intraperitoneally. Body weight gain, plasma levels of glucose and insulin, islet insulin secretion and content, lipid peroxidation and antioxidant status in the pancreas of rats were determined.

RESULTS

Compared to control group, the body weight gain and plasma insulin level were significantly decreased and plasma glucose and pancreatic NO and MDA concentrations and antioxidant enzymes activities were significantly increased in the STZ diabetic rats. In the diabetic rats, nitrate alone significantly reduced plasma glucose and increased pancreatic SOD and GPx activity. Reduced plasma glucose, pancreatic MDA and NO concentrations and increased plasma insulin level and pancreatic islet insulin secretion were observed in D + Ln and DN + Ln groups. Antioxidant enzymes activities were increased in diabetic rats which received combination of nitrate and L-NAME.

CONCLUSIONS

Our results showed that nitrate without effect on pancreatic islet insulin content and secretion decreased the blood glucose and slightly moderate oxidative stress and its effects in the presence of L-NAME on glucose hemostasis and pancreatic insulin secretion higher than those of nitrate alone.

摘要

目的

本研究旨在评估膳食硝酸盐在存在或不存在一氧化氮合酶抑制剂(L-精氨酸甲酯,L-NAME)的情况下,对链脲佐菌素(STZ)诱导的1型糖尿病大鼠胰岛分泌功能和氧化应激状态的影响。

方法

将50只成年雄性Sprague-Dawley大鼠分为5组:对照组(C)、糖尿病组(D)、糖尿病+硝酸盐组(DN)、糖尿病+L-NAME组(D+Ln)和糖尿病+硝酸盐+L-NAME组(DN+Ln),实验为期45天。饮用水中硝酸钠和腹腔注射L-NAME的浓度分别为80mg/L和5mg/kg。测定大鼠体重增加、血浆葡萄糖和胰岛素水平、胰岛胰岛素分泌和含量、胰腺脂质过氧化和抗氧化状态。

结果

与对照组相比,STZ糖尿病大鼠体重增加和血浆胰岛素水平显著降低,血浆葡萄糖、胰腺NO和丙二醛(MDA)浓度以及抗氧化酶活性显著增加。在糖尿病大鼠中,单独使用硝酸盐可显著降低血浆葡萄糖并增加胰腺超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)活性。在D+Ln和DN+Ln组中观察到血浆葡萄糖降低、胰腺MDA和NO浓度降低,血浆胰岛素水平和胰岛胰岛素分泌增加。接受硝酸盐和L-NAME联合治疗的糖尿病大鼠抗氧化酶活性增加。

结论

我们的结果表明,硝酸盐对胰岛胰岛素含量和分泌无影响,但可降低血糖并轻度减轻氧化应激,且在存在L-NAME的情况下,其对葡萄糖稳态和胰腺胰岛素分泌的影响高于单独使用硝酸盐。

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