Neuroprotective effect of PTEN inhibitor BPV on cerebral ischemia-reperfusion injury in rats and its mechanism
10.3760/cma.j.issn.1673-4165.2015.09.010
- VernacularTitle:TEN 抑制剂 BPV 对脑缺血再灌注损伤大鼠的神经保护作用及其机制
- Author:
Lunlin MAO
;
Donglin HAO
;
Xiaowei MAO
;
Tingting HUANG
;
Bona WU
- Publication Type:Journal Article
- Keywords:
Brain Ischemia;
Repefusion Injury;
PTEN Phosphohydrolase;
Vanadium Compounds;
Signal Transduction;
Phosphatidylinositol 3-Kinases;
Proto-Oncogene Proteins c-akt;
Glycogen Synthase Kinase 3;
Inflammation;
Neuroprotective Agents;
Rats
- From:
International Journal of Cerebrovascular Diseases
2015;(9):691-698
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigated the neuroprotective effect of PTEN inhibitor BPV on cerebral ischemia-reperfusion injury in rats and its mechanism. Methods Male Sprague-Dawley rats were used to induce a reperfusion model of middle cerebral artery occlusion for 1 h. During the reperfusion, the BPV solution (0. 2 mg/kg daily) or the equal volume of saline was injected intraperitonealy immediately. The neurological deficit scores were conducted at day 1, 3,5, and 7 after ischemia-reperfusion. At day 4, triphenyl tetrazolium chloride staining was used to assess cerebral infarction volume. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin 10 (IL-10) and tumor necrosis factor α(TNF-α) in cortical ischemic border zones. Real-time quantitative polymerase chain reaction was used to detect the expression level of PTEN mRNA. Western blotting was used to detect the expression levels of PI3K, Akt, and p-GSK-3β. At day 7, Bielschowsky silver staining was used to detect the axonal distribution in the ischemic border zone of the striatum. Immunohistochemical staining was used to detect the expression of myelin basic protein (MBP). Results At day 4 after ischemia-reperfusion, the infarct volume (32. 27% ± 1. 71% vs. 45. 49% ± 2. 12% ; P < 0. 001), TNF-α concentration in the cortical ischemic border zones (134. 17 ± 10. 38 pg/ml vs. 264. 17 ± 24. 84 pg/ml; P < ), and PTEN mRNA level (1. 19 ± 0. 08 vs. 2. 50 ± 0. 06; P < 0. 001) in the rats of the BPV group were al significantly lower than those of the normal saline group. The IL-10 concentration (186. 83 ± 10. 83 pg/ml vs. 147. 83 ± 11. 62 pg/ml; P < 0. 001), and the expression levels of PI3K (0. 43 ± 0. 08 vs. 0. 26 ± 0. 06; P = 0. 004), Akt (0. 52 ± 0. 05 vs. 0. 40 ± 0. 04;P = 0. 001), and p-GSK-3β (0. 75 ± 0. 08 vs. 0. 38 ± 0. 06; P < 0. 001) were al significantly higher than those of the normal saline group. At day 7 after ischemia-reperfusion, the neurological deficit score (4. 83 ± 0. 41 vs. 6. 33 ± 0. 52; P < 0. 001) in the rats of the BPV group was significantly lower than that of the normal saline group. The axon densities in the ischemic border zones (35. 51% ± 2. 45% vs. 25. 31% ± 2. 79% ; P < 0. 001) and the expression level of MBP (32. 56% ± 3. 46% vs. 27. 81% ± 4. 18% ; P = 0. 037) were significantly higher than those of the normal saline group. Conclusions BPV has neuroprotective effect for cerebral ischemia-reperfusion injury in rats. Its mechanism may be associated with the up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β expression to regulate inflammatory mediators and reduce the inflammatory response.
