Expressions of p-Akt (Ser473) and p-Bad (Ser136) and apoptosis in peri-infarction tissue following permanent middle cerebral artery occlusion in rats
10.3760/cma.j.issn.1673-4165.2013.08.006
- VernacularTitle:永久性大脑中动脉闭塞大鼠梗死周围组织p-Akt(Ser473)、p-Bad(Ser136)表达与细胞凋亡
- Author:
Min HE
;
Jiangquan HAN
;
Baiyun NI
;
Xianping ZHANG
- Publication Type:Journal Article
- Keywords:
Brain Ischemia;
Protein-Serine-Threonine Kinases;
Phosphatidy linositol 3-Kinases;
bcl-Associated Death Protein;
Proto-Oncogene Proteins c-akt;
Disease Models,Animal;
Apoptosis;
Rats
- From:
International Journal of Cerebrovascular Diseases
2013;21(8):624-629
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationship between the expression changes of p-Akt (Ser473),p-Bad (Ser136) and the cell apoptosis in peri-infarction tissue of permanent middle cerebral artery occlusion (MCAO) in rats.Methods Sixty male Sprague-Dawley rats were randomly allocated into sham operation,MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h,and LY294002 intervention MCAO 12 h groups (n =12 in each group).A permanent MCAO model was induced by the modified suture method.At 15 minutes before modeling,the rats in the LY294002 intervention MCAO groups were administered via lateral ventricle.The neurological function score was scored by using Zea Longa method.2,3,5-triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume.Immunohistochemical staining was use to detect pAkt (Ser473) and p-Bad (Ser136) expressions in peri-infaretion tissue.TUNEL assay was used to detect apoptotic cells in peri-infarction tissue.Results Three hours after modeling all the experimental rats awoke from anesthesia.The neurological deficit score in the sham operation group was 0,and the scores of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 2.25 ± 0.45,2.92 ± 0.99,3.00 ± 0.95,and 3.02 ± 0.36,respectively.There were significant differences among all groups (F =26.520,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly higher than that of the MCAO 3 h group (P =0.009).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P =0.354).TTC staining showed that no infarct was observed in the sham operation group.The infarct volumes of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 23.4 ± 1.4,40.3 ± 1.1,31.9 ±6.0 and 44.4 ±3.8 mm3,respectively.There were significant differences among the groups (F =30.440,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly greater than that of the MCAO 3 h group (P =0.002).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P=0.113).Compared with the sham operation group,the p-Akt (Ser473) expression in peri-infarction tissue in the MCAO 3 h group was significantly high,and it was significantly decreased in the MCAO 12 h group; the expression level of p-Bad (Ser136) showed a progressive decline with the passage of MCAO time,at the same time,the number of apoptotic cells increased progressively.After the LY294002 intervention,the expression levels of p-Akt (Ser473) and p-Bad (Ser136) in peri-infarction tissue decreased significantly at 3 h after MCAO,and the number of apoptotic cells increased significantly (P ＜0.05),but there was no significant effect on each index at 12 h after MCAO.Conclusions The activation of the PI3K/Akt signal transduction pathway in early cerebral infarction and the stress elevation of the key protein p-Akt (Ser473) of this pathway have brain protection,while the failure of this pathway activity and the drastical decrease of its key protein in the late cerebral infarction are associated with brain injury.
