Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat

被引:8
作者
Yang, Yang [1 ]
Chen, Qi [2 ]
Zhao, Quanfeng [3 ]
Luo, Ying [1 ]
Xu, Ying [4 ]
Du, Weimin [1 ]
Wang, Hong [1 ]
Li, Huan [1 ]
Yang, Lu [1 ]
Hu, Congli [1 ]
Zhang, Jiahua [1 ]
Li, Yuke [1 ]
Xia, Hui [1 ]
Chen, Zhihao [1 ]
Ma, Jie [1 ]
Tian, Xiaoyan [1 ]
Yang, Junqing [1 ]
机构
[1] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol, Dept Pharmacol, Chongqing, Peoples R China
[2] GuiZhou Prov Peoples Hosp, Dept Pharm, Guiyang, Guizhou, Peoples R China
[3] Army Med Univ, Mil Med Univ 3, Affiliated Hosp TMMU 1, Southwest Hosp,Dept Pharm, Chongqing, Peoples R China
[4] SUNY Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, Buffalo, NY USA
来源
FRONTIERS IN CELLULAR NEUROSCIENCE | 2019年 / 13卷
关键词
cyclooxygenase-2; PGD2; type; 2; diabetes; brain injury; autophagy; ACTIVATED PROTEIN-KINASE; ENDOPLASMIC-RETICULUM STRESS; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; COGNITIVE DECLINE; SIGNALING PATHWAY; GLUCOSE; INFLAMMATION; APOPTOSIS; MEMORY;
D O I
10.3389/fncel.2019.00068
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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), A beta, 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, A beta, 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, A beta, 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.
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页码:1 / 11
页数:11
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