艾司洛尔对脓毒症大鼠心肌保护作用及其可能机制  

MYOCARDIAL PROTECTIVE EFFECT OF ESMOLOL IN SEPTIC RATS AND ITS POSSIBLE MECHANISM

作　　者：白雪[1] 杨冰心[1] 赵婉君[1] 山峰[1] 王春朋 BAI Xue;YANG Bingxin;ZHAO Wanjun;SHAN Feng;WANG Chunpeng(Intensive Care Unit,The Affiliated Hospital of Qingdao Univer-sity,Qingdao 266100,China)

机构地区：[1]青岛大学附属医院重症医学科,山东青岛266100

出　　处：《青岛大学学报（医学版）》2021年第1期120-124,共5页Journal of Qingdao University(Medical Sciences)

基　　金：青岛市医药科研指导计划项目(2016-WJZD026)。

摘　　要：目的探讨艾司洛尔对脓毒症大鼠的心肌保护作用及对Toll样受体4(TLR4)/髓样分化蛋白88(Myd88)/核因子-κB(NF-κB)蛋白通路的调控。方法选取雄性SD大鼠60只,采用随机数字法随机分为假手术组(Sham组)、脓毒症组(Model组)、艾司洛尔组(ES组),每组20只。Sham组实施盲肠探查术,Model组、ES组采用盲肠结扎穿孔术(CLP法)建立脓毒症模型;ES组持续微量泵入艾司洛尔稀释液1 mL/h(15 mg·kg^-1·h^-1),共6 h,Sham组和Model组泵入等量生理盐水。各组均于术后24 h检测血清中肌钙蛋白I(TnI)、肿瘤坏死因子α(TNF-α)、白细胞介素-1(IL-1)的表达,取左心室游离壁行苏木精-伊红染色观察心肌病理学变化,采用Western blot法检测心肌组织TLR4、Myd88及NF-κB的表达。结果与Sham组相比,Model组心肌病理损伤明显加重,心肌损伤指标TnI水平和炎症递质TNF-α及IL-1水平明显升高;与Model组相比,ES组心肌损伤明显减轻,炎症递质水平明显降低,差异均有显著性(F=18.84~602.11,P<0.05)。Western blot检测显示,Model组心肌组织中TLR4、Myd88及NF-κB蛋白表达水平较Sham组明显升高,而ES组心肌组织中三者表达较Model组明显降低,差异均有显著性(F=17.15~95.92,P<0.05)。结论艾司洛尔能够减轻炎症反应和心肌损伤,其作用机制可能与抑制TLR4/Myd88/NF-κB信号通路的激活有关。Objective To investigate the myocardial protective effect of esmolol in septic rats and its regulation of the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(Myd88)/nuclear factor-kappa B(NF-κB)pathway.Methods Sixty male SD rats were selected and randomly divided into sham-operation group(sham group),sepsis group(model group),and esmolol group(ES group),with 20 rats in each group.The sham group underwent cecum exploration,and the model group and ES group underwent cecal ligation and puncture to establish a model of sepsis.The ES group received continuous micropumping of diluted esmolol solution at 1 mL/h(15 mg·kg^-1·h^-1)for 6 h,while the sham group and model group received micropumping of an equal volume of normal saline.At 24 hours after operation,each group was tested for the expression of troponin I(TnI),tumor necrosis factorα(TNF-α),and interleukin-1(IL-1)in serum;the left ventricular free wall was taken for hematoxylin and eosin staining to observe the pathological changes in the myocardium;Western blot was used to determine the expression of TLR4,Myd88,and NF-κB in the myocardial tissue.Results Compared with sham group,the model group had significantly more severe pathological myocardial injury,with significantly increased myocardial injury index TnI and inflammatory mediators TNF-αand IL-1.Compared with the model group,the ES group had significantly reduced myocardial injury and inflammatory mediators(F=18.84-602.11,P<0.05).Western blot showed that the protein expression levels of TLR4,Myd88,and NF-κB in the model group was significantly higher than those in the sham group,while the above indices were significantly lower in the ES group than in the model group(F=17.15-95.92,P<0.05).Conclusion Esmolol can reduce inflammatory response and myocardial injury,the mechanism of which may be associated with inhibiting activation of the TLR4/Myd88/NF-κB signaling pathway.

关 键 词：脓毒症 肾上腺素能Β受体拮抗剂 TOLL样受体4 髓样分化因子88 NF-κB 大鼠 

分 类 号：R631[医药卫生—外科学] R971.93[医药卫生—临床医学]