12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis

作者全名："Chen, Qi; Zheng, Qixue; Yang, Yang; Luo, Ying; Wang, Hong; Li, Huan; Yang, Lu; Hu, Congli; Zhang, Jiahua; Li, Yuke; Xia, Hui; Chen, Zhihao; Ma, Jie; Tian, Xiaoyan; Yang, Junqing"

作者地址："[Chen, Qi; Zheng, Qixue; Luo, Ying; Wang, Hong; Li, Huan; Yang, Lu; Hu, Congli; Zhang, Jiahua; Li, Yuke; Xia, Hui; Chen, Zhihao; Ma, Jie; Tian, Xiaoyan; Yang, Junqing] Chongqing Med Univ, Dept Pharmacol, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Chen, Qi] Guizhou Prov Peoples Hosp, Pharm Dept, Guiyang 550002, Peoples R China; [Chen, Qi; Yang, Yang] Chongqing Hlth Ctr Women & Children, Dept Pharmacol, Chongqing 400016, Peoples R China; [Yang, Junqing] Chongqing Med Univ, Dept Pharmacol, Chongqing 400016, Peoples R China"

通信作者："Yang, JQ (通讯作者)，Chongqing Med Univ, Dept Pharmacol, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China.; Yang, JQ (通讯作者)，Chongqing Med Univ, Dept Pharmacol, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000846564700001

JCR分区：Q2

影响因子：5.6

年份：2022

卷号：23

期号：16

开始页：　

结束页：　

文献类型：Article

关键词：12; 15-lipoxygenase; regulation; diabetic cognitive dysfunction; inflammation; cell apoptosis

摘要："This study aimed to discuss the role of 12/15-lipoxygenase (12/15-LOX) regulation involved in diabetes cognitive dysfunction. First, Mini Mental State Examination (MMSE) test was used to evaluate cognitive ability in diabetic patients and normal controls. The plasma test showed that the plasma level of 12/15-LOX in patients with MMSE scores below 27 was significantly increased compared with that of the normal group. Second, 12/15-LOX inhibitor was administered to diabetic rats. Behavioral tests, biochemistry, enzyme-linked immunosorbent assays, and Western blotting were used in this study. We found that the levels of fasting and random blood glucose increased rapidly in diabetic rats, the levels of triglycerides and total cholesterol in the diabetic group increased, and insulin levels decreased significantly. In the Morris water maze test, the escape latency was prolonged, and the crossing times decreased in the diabetic group. Under the microscope, the apoptosis of hippocampal neurons in diabetic rats increased significantly. The levels of TNF-alpha, IL-6 and 12-hydroxyindoleic acid (12(S)-HETE) significantly increased, and the protein expression of 12/15-LOX, p38 MAPK, A beta(1-42), caspase-3, caspase-9 and cPLA2 increased, while that of Bcl-2 decreased. However, the use of 12/15-LOX inhibitor reversed these results. Third, 12/15-LOX shRNA and p38MAPK inhibitor were administered to HT22 cells in high-glucose medium. The results of the cell experiment were consistent with those of the animal experiment. Our results indicated that the 12/15-LOX pathway participates in diabetic brain damage by activating p38MAPK to promote inflammation and neuronal apoptosis, and intervention 12/15-LOX can improve diabetic cognitive dysfunction."

基金机构：Funding Program for Youth of Guizhou provincial people's hospital [GZSYQN [2016]17]; Science and Technology Program of Guizhou province [QIANKEHE [2019]1191]

基金资助正文：This research was funded by Funding Program for Youth of Guizhou provincial people's hospital (GZSYQN [2016]17) and Science and Technology Program of Guizhou province (QIANKEHE [2019]1191).