脂联素通过抑制线粒体融合分裂不平衡改善慢性间歇性缺氧诱导的胰岛损伤。

Can He, Xi-Long Zhang, Qiang Zhang, Lu-Yao Ge, Wen-Xiao Ding
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引用次数: 0

摘要

目的探讨脂联素(APN)对慢性间歇性缺氧(CIH)所致胰岛损伤的保护作用。方法将60只大鼠随机分为正常对照(NC)组、CIH组、CIH加APN (CIH+APN)组。暴露于CIH 5周后,进行口服糖耐量试验(OGTT)和胰岛素释放试验(IRT),检测并比较三磷酸腺苷(ATP)水平、线粒体膜电位(MMP)水平、活性氧(ROS)水平、代表线粒体三羧酸循环功能的Ant1、Cs、Hmox1、Cox4i1酶基因表达水平、DRP1、FIS1、MFN1、和代表线粒体融合分裂的OPA1,以及代表胰岛线粒体相关凋亡途径的BAX、BCL-2、cleaved Caspase-3和cleaved PARP的蛋白表达水平。结果OGTT和IRT显示,NC组、CIH组和CIH+APN组在0、20、30、60、120 min时血糖和胰岛素水平无显著差异(P>0.05),但我们发现与NC组相比,CIH组ROS水平升高,ATP水平和MMP水平降低。CIH暴露大鼠胰岛Ant1、Cs、Hmox1、Cox4i1基因表达水平降低,MFN1、OPA1蛋白和基因表达水平降低,DRP1、FIS1蛋白和基因表达水平升高,裂解Caspase-3、裂解PARP蛋白表达水平升高,蛋白表达水平下BCL-2/BAX比值降低。三组间差异均有统计学意义。APN处理的CIH大鼠显示与胰岛损伤相关的上述测量变化减轻。结论APN可能通过抑制线粒体融合分裂失衡,改善CIH所致胰岛损伤。
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Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

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