摘要
探讨丙泊酚对心肌再灌注大鼠的保护作用及对NOD样受体蛋白3(NLRP3)/半胱天冬酶-1(caspase-1)通路的影响。方法SPF级雄性SD大鼠60只,随机分为6组:对照组、模型组(造模前股静脉注射生理盐水3 mL/kg)、NLRP3抑制剂组(造模前股静脉注射CY-095 mg/kg),丙泊酚低、中、高剂量组(造模前大鼠股静脉分别注射丙泊酚20、40、60 mg/kg)。除对照组外,均采用结扎左冠状动脉前降支(LAD)法制备心肌再灌注模型。再灌注结束即刻采用氯化三苯四氮唑(TTC)法测心肌梗死面积百分比,苏木素伊红(HE)染色观察心肌形态学改变;黄嘌呤氧化酶法检测超氧化物歧化酶(SOD),采用硫代巴比妥酸比色法检测丙二醛(MDA)含量;酶联免疫法(ELISA)检测大鼠心肌中白细胞介素–1(IL-1)、肿瘤坏死因子(TNF-α)水平;采用Western blot法检测心肌NLRP3、caspase-1、凋亡相关斑点样蛋白(ASC)的表达水平。结果与对照组比较,模型组心肌病理变化损伤严重,心肌梗死面积百分比升高,MDA含量升高,SOD含量降低,心肌组织中NLRP3、caspase-1、ASC和IL-1β、TNF-α蛋白表达均显著上调(P<0.05)。与模型组比较,NLRP3抑制剂组、丙泊酚低、中、高剂量组大鼠心肌病理损伤减轻,心肌梗死面积百分比降低,MDA含量降低,SOD含量升高,心肌NLRP3、caspase-1、ASC和IL-lβ、TNF-α表达下调(P<0.05)。结论丙泊酚可通过降低NLRP3/caspase-1通路,减少炎症因子IL-lβ、TNF-α释放,对心肌再灌注损伤大鼠起一定保护作用。
Objective To explore the effect of propofol on the protection against myocardial reperfusion injury and on NOD-like receptor protein 3(NLRP3)/caspase-1 signal pathway in rats.Methods Sixty specific pathogen free(SPF)male Sprague-Dawley(SD)rats were treated before the construction of myocardial reperfusion injury model(by ligation of left anterior descending coronary[LAD]for all the rats except for those of control group)with different agents via femoral vein injection and then randomly divided into six groups:a control group and a model group(both with 3 ml/kg normal saline),a NLRP3 inhibitor group(with 5 mg/kg CY-09),and low-,moderate-high-dose groups(with 20,40,60 mg/kg propofol),respectively.Two hours after the construction of myocardial reperfusion injury model,the percentage of myocardial infarction area was measured by triphenyltetrazolium chloride(TTC)method;morphological changes of myocardial tissues were observed with hematoxylin-eosin(HE)staining;and following reperfusion injury related indicators in myocardial tissues were determined:superoxide dismutase(SOD)with xanthine oxidase method,malondialdehyde(MDA)with thiobarbituric acid colorimetry,interleukin-1(IL-1)/tumor necrosis factor(TNF-α)with enzyme-linked immunosorbent assay(ELISA),and NLRP3/caspase-1/apoptosis-associated speck-like protein(ASC)with Western blot.Results Compared to those in the control rats,increased myocardial infarction area and severe pathological changes of myocardial tissues were observed and decreased SOD content but increased MDA content and NLRP3,caspase-1,ASC,IL-lβand TNF-αexpressions in myocardium were detected in the model rats(P<0.05 for all).The rats in the NLRP3 inhibitor group and in the three groups with propofol treatment had significantly alleviated myocardial pathological changes,decreased myocardial infarction area,increased SOD,decreased MDA,and down-regulated expressions of of NLRP3,caspase-1,ASC,IL-lβand TNF-αin comparison to the rats of model group(all P<0.05).Conclusion Propofol may play a protective ro
作者
张剑锋
王平
刘维
ZHANG Jian-feng;WANG Ping;LIU Wei(Anesthesiology Department,Affiliated Nanhua Hospital of University of South China,Hengyang,Hunan Province 421002,China;不详)
出处
《中国公共卫生》
CAS
CSCD
北大核心
2020年第9期1313-1317,共5页
Chinese Journal of Public Health
