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内吗啡肽对胰岛氧化损伤的保护作用。

A protective effect of endomorphins on the oxidative injury of islet.

作者信息

Tian L M, Liu J, Sun X L, Gao C X, Fan Y, Guo Q

机构信息

Department of Endocrinology, People's Hospital of Gansu Province, Lanzhou, PR China.

出版信息

Exp Clin Endocrinol Diabetes. 2010 Aug;118(8):467-72. doi: 10.1055/s-0030-1252068. Epub 2010 Apr 28.

Abstract

The antioxidative capacity of endomorphins (EMs), endogenous μ-opioid receptor agonists, has been demonstrated by IN VIVO assays. In this study, we attempt to evaluate the effects of endomorphin 1 (EM1) and endomorphin 2 (EM2) on pancreatic islet injuries induced by streptozotocin (STZ), alloxan (ALX) and H(2)O(2), respectively. Wistar rats' islets were isolated and purified. The function of the islet cells, the insulin response to glucose stimulation was examined by insulin Radio Immuno Assay and the cell viability was measured by MTT assay. DNA fragments were performed to evaluate the apoptosis, while the cell cycle distribution was analyzed by PI staining flow cytometric analysis. Furthermore, the islet were treated with EM1, EM2 or ALX for 24 h, and the expression of p53 and p21 protein were determined by Western blot. The results showed that STZ, ALX, and H(2)O(2) displayed clear concentration-dependent inhibitory effects on the pancreatic islet cells. While EMs improved the viability of islet induced by STZ, ALX or H(2)O(2), and EMs enhanced insulin accumulation of the cell supernatant after ALX and STZ stimulation. Our data also showed both that EMs inhibited cell apoptosis and cell cycle G1 arrest induced by STZ and ALX through down-regulaing p53 and p21 expression. Taken together, these results demonstrate that EMs can protect islet cells from STZ, ALX and H(2)O(2) induced injuries. Our observations imply that the endomorphins may have protective effects on islet cells oxidative injury.

摘要

内吗啡肽(EMs)作为内源性μ-阿片受体激动剂,其抗氧化能力已通过体内实验得到证实。在本研究中,我们试图分别评估内吗啡肽-1(EM1)和内吗啡肽-2(EM2)对链脲佐菌素(STZ)、四氧嘧啶(ALX)和过氧化氢(H₂O₂)诱导的胰岛损伤的影响。分离并纯化Wistar大鼠的胰岛。通过胰岛素放射免疫分析法检测胰岛细胞功能及葡萄糖刺激后的胰岛素反应,采用MTT法测定细胞活力。进行DNA片段分析以评估细胞凋亡情况,通过PI染色流式细胞术分析细胞周期分布。此外,将胰岛用EM1、EM2或ALX处理24小时,通过蛋白质免疫印迹法测定p53和p21蛋白的表达。结果表明,STZ、ALX和H₂O₂对胰岛细胞呈现明显的浓度依赖性抑制作用。而EMs可提高由STZ、ALX或H₂O₂诱导损伤的胰岛的活力,并且EMs可增强ALX和STZ刺激后细胞上清液中的胰岛素积累。我们的数据还显示,EMs通过下调p53和p21的表达,抑制了由STZ和ALX诱导的细胞凋亡及细胞周期G1期阻滞。综上所述,这些结果表明EMs可保护胰岛细胞免受STZ、ALX和H₂O₂诱导的损伤。我们的观察结果提示,内吗啡肽可能对胰岛细胞氧化损伤具有保护作用。

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