Wu Yini, Wang Jianping, Yu Xiaoyan, Li Dongli, Han Xin, Fan Lihua
Department of General surgery,Wenzhou Medical College, the fifth Affiliated Hospital.
Cardiol J. 2017;24(4):409-418. doi: 10.5603/CJ.a2017.0018. Epub 2017 Feb 15.
The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mam-malian target of rapamycin (mTOR) signaling pathway.
Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-μL saline solution), sevoflurane group (SevG, inhaled with 2.4% sevoflurane for 2 h), LY294002 group (LYG, Akt inhibitor, 0.3 mg/kg in 200-μL Dimethyl Sulfoxide [DMSO]), solvent DMSO control group (SG) and autophagy inhibitor 3-methyladenine (3-MA) group (MG, 30 mg/kg in 200-μL DMSO). The healthy rats were assigned to a contro1 group (CG, 200-μL saline solution). Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The concentration of cardiac troponin I (cTnI) was detected by ELISA. The levels of total Akt (t-Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR) and autophagy marker LC3-II was detected by Western Blot. The experiments were also repeated at the cell level.
Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis showed that the ap-optosis rates were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG. The levels of p-Akt p-mTOR were low in groups DG and SG, reached the lowest level in LYG, increased in SevG and MG, and reached the highest level in CG. In contrast, LC3-II expression, apoptosis index and serum cTnI concentration were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG (p < 0.05). Cell experiment showed similar results as with animal experiments.
Sevoflurane ameliorates myocardial injury by affecting the phosphorylation states of the proteins in PI3K/Akt/mTOR signaling pathway and reducing the injury biomarker. (Cardiol J 2017; 24, 4: 409-418).
通过研究磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路中蛋白质的磷酸化状态，探讨七氟醚对阿霉素诱导的心肌损伤的影响。
采用阿霉素诱导建立心肌损伤大鼠模型，并根据不同处理将其平均分为五组：阿霉素组（DG，200 μL生理盐水）、七氟醚组（SevG，吸入2.4%七氟醚2小时）、LY294002组（LYG，Akt抑制剂，0.3 mg/kg溶于200 μL二甲基亚砜[DMSO]）、溶剂DMSO对照组（SG）和自噬抑制剂3-甲基腺嘌呤（3-MA）组（MG，30 mg/kg溶于200 μL DMSO）。将健康大鼠作为对照组（CG，200 μL生理盐水）。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测心肌细胞凋亡。采用酶联免疫吸附测定法（ELISA）检测心肌肌钙蛋白I（cTnI）浓度。采用蛋白质免疫印迹法检测总Akt（t-Akt）、磷酸化Akt（p-Akt）、雷帕霉素哺乳动物靶蛋白（mTOR）、磷酸化mTOR（p-mTOR）和自噬标志物微管相关蛋白1轻链3-II（LC3-II）的水平。细胞水平实验也重复进行。
TUNEL分析显示，DG组和SG组凋亡率较高，LYG组达到最高水平，SevG组和MG组降低，CG组达到最低水平。DG组和SG组中p-Akt、p-mTOR水平较低，LYG组达到最低水平，SevG组和MG组升高，CG组达到最高水平。相反，DG组和SG组中LC3-II表达、凋亡指数和血清cTnI浓度较高，LYG组达到最高水平，SevG组和MG组降低，CG组达到最低水平（p<0.05）。细胞实验结果与动物实验相似。
七氟醚通过影响PI3K/Akt/mTOR信号通路中蛋白质的磷酸化状态并降低损伤生物标志物水平，改善心肌损伤。（《心脏病学杂志》2017年；24卷，第4期：409 - 418页）
