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  

Role of PI3K/Akt signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in rats

作　　者：武旖旎 韩新[1] 樊理华[1] 

机构地区：[1]温州医科大学附属第六医院丽水市人民医院麻醉科,丽水市323000

出　　处：《中华麻醉学杂志》2016年第6期728-731,共4页Chinese Journal of Anesthesiology

基　　金：浙江省卫生厅平台重点项目（2014ZDA031）;丽水市高层次人才培养资助项目（2013RC04）

摘　　要：目的评价磷脂酰肌醇-3激酶／蛋白质丝氨酸苏氨酸激酶（P1I3K／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。方法清洁级健康雄性SD大鼠36只，体重200～250g，采用随机数字表法分为6组（n=6）：对照组（C组）、阿霉素致心肌损伤组（Dox组）、七氟醚组（Sev组）、P13K抑制剂LY294002组（LY组）、溶剂对照组（DMSO组）和自噬抑制剂3-MA组（3-MA组）。除C组外，其余5组制备阿霉素致大鼠心肌损伤模型。C组与Dox组单纯机械通气2h；Sev组吸入2．4％七氟醚2h；LY组于麻醉前10min尾静脉注射LY2940020．3mg／kg，吸入2．4％七氟醚2h；DMSO组注射同等剂量DMSO，吸入2．4％七氟醚2h；3-MA组于麻醉前10min腹腔注射30mg／kg自噬抑制剂3-MA，吸入2．4％七氟醚2h。心脏采血后处死大鼠取心肌，采用ELISA法测定血清cTnI浓度；Western blot法检测总Akt（t-Akt）、磷酸化Akt（p-Akt）、雷帕霉素靶蛋白（mTOR）、磷酸化mTOR（p-mTOR）及自噬标记物微管相关蛋白1轻链3Ⅱ（LC3Ⅱ）的表达；TUNEL法检测细胞凋亡情况，计算细胞凋亡指数。结果与C组比较，其余5组心肌p-Akt和p-mTOR的表达下调，LC3Ⅱ表达上调，细胞凋亡指数和血清cTnI浓度升高（P〈0．05）；与Dox组比较，Sev组心肌p-Akt和p-mTOR的表达上调，LC3Ⅱ表达下调，细胞凋亡指数和血清cTnI浓度降低（P〈0．05）；与Sev组比较，LY组心肌p-Akt和p-mTOR的表达下调，LC3Ⅱ表达上调，细胞凋亡指数和血清cTnI浓度升高，3-MA组LC3Ⅱ表达下调，血清eTnI浓度降低（P〈0．05）。结论七氟醚通过激活P13K／Akt信号通路和抑制自噬减轻阿霉素致大鼠的心肌损伤。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）, adriartlyein-induced myocardial injury group （group Dox）, sevoflurane group （group Sev）, LY294002 inhibitor group （group LY）, solvent control group （group dimethyl sulfoxide I 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 microtubuleassociated protein light chain 3 H （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-roTOR was significantly up-regulated, and the expression of LC

关 键 词：麻醉药 吸入 磷脂酰肌醇-3激酶 蛋白质丝氨酸苏氨酸激酶 自噬 

分 类 号：R614[医药卫生—麻醉学]