Role of PI3K/Akt signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in rats
10.3760/cma.j.issn.0254-1416.2016.06.021
- VernacularTitle:PI3K/Akt信号通路和自噬在七氟醚减轻阿霉素致大鼠心肌损伤中的作用
- Author:
Yini WU
;
Xin HAN
;
Lihua FAN
- Publication Type:Journal Article
- Keywords:
Anesthetics,inhalation;
Phosphatidylinositol 3-kinase;
Protein-serine-threonine kinases;
Autophagy
- From:
Chinese Journal of Anesthesiology
2016;36(6):728-731
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K/Akt) signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in the rats.Methods Thirty-six healthy male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =6 each) using a random number table:control group (group C),adriamycin-induced myocardial injury group (group Dox),sevoflurane group (group Sev),LY294002 inhibitor group (group LY),solvent control group (group dimethyl sulfoxide [DMSO]),and 3-MA inhibitor group (group 3-MA).Adriamycin 4 mg/kg was injected intraperitoneally once a week for 3 weeks in all the groups except group C.The rats were mechanically ventilated for 2 h in C and Dox groups.The rats inhaled 2.4％ sevoflurane for 2 h in group Sev.In group LY,0.3 mg/kg LY294002 was injected via the tail vein at 10 min before anesthesia,and the rats inhaled 2.4％ sevoflurane for 2 h.In group DMSO,the equal volume of DMSO was injected,and the rats inhaled 2.4％ sevoflurane for 2 h.After the blood samples were collected from the heart,the rats were sacrificed,and myocardial specimens were obtained for determination of cardiac troponin Ⅰ (cTnI) concentrations in serum (by enzyme-linked immunosorbent assay),expression of total Akt (t-Akt),phosphorylated Akt (p-Akt),mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and autophagy marker microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ) (by Western blot),and cell apoptosis (by TUNEL).Apoptosis index (AI) was calculated.Results Compared with group C,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in the other five groups (P＜ 0.05).Compared with group Dox,the expression of p-Akt and p-mTOR was significantly up-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly decreased in group Sev (P＜0.05).Compared with group Sev,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in group LY,and the expression of LC3 Ⅱ was significantly down-regulated,and serum cTnI concentrations were significantly decreased in group 3-MA (P＜0.05).Conclusion Sevoflurane can activate PI3K/Akt signaling pathway and inhibit autophagy,thus reducing adriamycin-induced myocardial injury in rats.
