Yang Yang, Chen Qi, Zhao Quanfeng, Luo Ying, Xu Ying, Du Weimin, Wang Hong, Li Huan, Yang Lu, Hu Congli, Zhang Jiahua, Li Yuke, Xia Hui, Chen Zhihao, Ma Jie, Tian Xiaoyan, Yang Junqing
Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, China.
Department of Pharmacy, GuiZhou Provincial People's Hospital, Guiyang, China.
Front Cell Neurosci. 2019 Feb 27;13:68. doi: 10.3389/fncel.2019.00068. eCollection 2019.
The present study was designed to observe the effect of COX2/PGD2-related autophagy on brain injury in type 2 diabetes rats. The histopathology was detected by haematoxylin-eosin staining. The learning and memory functions were evaluated by Morris water maze. The levels of insulin and PGD2 were measured by enzyme-linked immunosorbent assay. The expressions of COX2, p-AKT(S473), p-AMPK(T172), Aβ, Beclin1, LC3BII, and p62 were measured by immunohistochemistry and Western blotting. In model rats, we found that the body weight was significantly decreased, the blood glucose levels were significantly increased, the plasma insulin content was significantly decreased, the learning and memory functions were impaired and the cortex and hippocampus neurons showed significant nuclear pyknosis. The levels of COX2, p-AKT(S473), PGD2, Aβ, Beclin1 and p62 were significantly increased, whereas the expression of p-AMPK(T172) and LC3BII was significantly decreased in the cortex and hippocampus of model rats. In meloxicam-treated rats, the body weight, blood glucose and the content of plasma insulin did not significantly change, the learning and memory functions were improved and nuclear pyknosis was improved in the cortex and hippocampus neurons. The expression of p-AMPK(T172), Beclin1 and LC3BII was significantly increased, and the levels of COX2, p-AKT(S473), PGD2, Aβ, and p62 were significantly decreased in the cortex and hippocampus of meloxicam-treated rats. Our results suggested that the inhibition of COX2/PGD2-related autophagy was involved in the mechanism of brain injury caused by type 2 diabetes in rats.
本研究旨在观察COX2/PGD2相关自噬对2型糖尿病大鼠脑损伤的影响。通过苏木精-伊红染色检测组织病理学变化。采用Morris水迷宫评估学习和记忆功能。通过酶联免疫吸附测定法测量胰岛素和PGD2水平。采用免疫组织化学和蛋白质印迹法检测COX2、p-AKT(S473)、p-AMPK(T172)、Aβ、Beclin1、LC3BII和p62的表达。在模型大鼠中，我们发现体重显著降低，血糖水平显著升高，血浆胰岛素含量显著降低，学习和记忆功能受损，皮质和海马神经元出现明显的核固缩。模型大鼠皮质和海马中COX2、p-AKT(S473)、PGD2、Aβ、Beclin1和p62水平显著升高，而p-AMPK(T172)和LC3BII的表达显著降低。在美洛昔康治疗的大鼠中，体重、血糖和血浆胰岛素含量无显著变化，学习和记忆功能得到改善，皮质和海马神经元的核固缩情况有所改善。美洛昔康治疗的大鼠皮质和海马中p-AMPK(T172)、Beclin1和LC3BII的表达显著增加，而COX2、p-AKT(S473)、PGD2、Aβ和p62的水平显著降低。我们的结果表明，抑制COX2/PGD2相关自噬参与了大鼠2型糖尿病所致脑损伤的机制。
