摘要
目的评价α7烟碱能乙酰胆碱受体（α7nAChR）激动剂后处理及其联合肢体远隔缺血后处理抑制大鼠心肌缺血再灌注时炎症反应的机制与糖原合成酶激酶-3β（GSK-3β）的关系。
方法成年雄性SD大鼠80只，8周龄，体重290～320 g，采用随机数字表法分成4组（n＝20）：心肌缺血再灌注组（I/R组）、α7nAChR激动剂后处理组（P组）、肢体远隔缺血后处理组（L组）和α7nAChR激动剂后处理＋肢体远隔缺血后处理组（P＋L组）。采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备心肌缺血再灌注损伤模型。P组再灌注前即刻静脉注射特异性α7nAChR激动剂PNU282987 2 mg/kg；L组于心肌缺血20 min时采用止血带结扎双侧后肢缺血10 min，心肌再灌注开始时松开后肢结扎；P＋L组联合应用P组和L组的干预措施。再灌注120 min时采集静脉血样，采用ELISA法检测血清cTnI和CK-MB浓度；采用伊文氏蓝和TTC双染色法确定心肌梗死面积（IS）；采用Western blot法检测心肌磷酸化GSK-3β[p-GSK-3β（Ser536）]、NF-κBp65和磷酸化NF-κBp65（p-NF-κBp65）的表达。
结果与I/R组比较，P组、L组和P＋L组心肌IS、血清cTnI和CK-MB浓度降低，缺血区心肌p-GSK-3β（Ser9）表达上调，p-NF-κBp65表达下调（P〈0.05）；与L组比较，P＋L组心肌IS、血清cTnI和CK-MB浓度降低，缺血区心肌p-GSK-3β（Ser9）表达上调，p-NF-κBp65表达下调（P〈0.05）。
结论α7nAChR激动剂后处理及其联合肢体远隔缺血后处理抑制大鼠心肌缺血再灌注时炎症反应的机制可能与抑制GSK-3β活性有关。
Objective To evaluate the relationship between the mechanism underlying inhibition of inflammatory responses induced by ct7 nicotinic acetylcholine receptor （ct7nAChR） agonist postcondition- ing alone or in combination with remote limb ischemic postconditioning during myocardial ischemia-reperfu- sion （I/R） and glycogen synthase kinase-3β （GSK-3β） in rats. Methods Eighty adult male Sprague- Dawley rats, aged 8 weeks, weighing 290-320 g, were divided into 4 groups （n=20 each） using a ran-dom number table ： I/R group, a 7nAChR agonist postconditioning group （ group P）, remote limb ische- mic postconditioning group （group L） and a 7nAChR agonist postconditioning plus remote limb ischemic postconditioning group （group P＋L）. Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of coronary artery followed by 120 min reperfusion. Specific a 7nAChR agonist PNU282987 2 mg/kg was intravenously injected immediately before reperfusion in group P. In group L, limb ischemia was induced by tourniquet occlusion of bilateral hind paws for 10 min starting from 20 min of myocardial ischemia, and the tourniquet was released at the beginning of reperfusion. Combination of inter- vention measures previously described in P and L groups was performed in group P＋L. Venous blood sam- ples were t .aken at 120 min of reperfusion for determination of serum troponin I （TnI） and creatine kinase- MB （CK-MB） concentrations, myocardial infarct size （iS） and expression of phosphorylated GSK-3β [ p-GSK-3β （Ser536） ], NF-KBp65 and phosphorylated nuclear factor-KBp65 （p-NF-KBp65） in myocar- dial tissues （by Western blot）. Results Compared with group I/R, myocardial IS and serum cTnI and CK-MB concentrations were significantly decreased, the expression of p-GSK-3β （Ser9） in ischemic area was up-regnlated, and the expression of p-NF-KBp65 in ischemic area was down-regulated in P, L and P＋ L groups （P〈0. 05）. Compared with group L, myocardial IS a
作者
崔昕龙
王世玉
薛富善
杨桂珍
李慧娴
刘亚洋
廖旭
Cui Xinlong, Wang Shiyu, Xue Fushan, Yang Guizhen, Li Huix- ian, Liu Yayang, Liao Xu(Department of Anesthesiology, Plastic Surgery Hospital Chinese Academy of Medical Sciences Peking U- nion Medical College, Beifing 100144, China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2018年第1期78-82,共5页
Chinese Journal of Anesthesiology
基金
国家自然科学基金（81170128,81470019）
关键词
心肌再灌注损伤
炎症
糖原合成酶激酶3
胆碱能激动剂
四肢
缺血后
处理
Myocardial reperfusion injury
Inflammation
Glycogen synthase kinase 3
Cho-linergic agonists
Extremities
Ischemic postconditioning
