早期应用艾司洛尔对脓毒症大鼠心肌损伤的实验研究  

Early effects of esmolol on myocardial injury in rats with sepsis

作　　者：董小荣[1] 方德舟 张蓓[1] 王映珍[1] 马莉[1] Dong Xiao-rong;Fang De-zhou;Zhang Bei;Wang Ying-zhen;Ma Li(Department of Emergency Intensive Care Unit,The Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二医院急诊ICU,甘肃兰州730030

出　　处：《兰州大学学报（医学版）》2018年第4期33-39,共7页Journal of Lanzhou University（Medical Sciences）

基　　金：北京协和医学基金会睿E(睿意)急诊医学研究专项基金项目(R2015003).

摘　　要：目的研究早期应用β1受体阻滞剂艾司洛尔对脓毒症大鼠心肌损伤的作用。方法72只SD雄性大鼠,分为3组:假手术组(Sham组)、脓毒症组(CLP组)、艾司洛尔组(ES组),每组24只;各组随机抽取6只观察7天生存情况,剩余18只又分为6、12、24 h 3个亚组,每个亚组6只。Sham组采用盲肠探查术,CLP组、ES组采用盲肠结扎穿孔法建立脓毒症模型。造模成功后行左侧颈内静脉置管。Sham组、CLP组持续微量泵泵入生理盐水1 mL/h,共计6 h;ES组持续泵入艾司洛尔稀释液1 m L/h[15 mg/(kg·h)],共计6 h。亚组均于时间点处死大鼠,采用ELISA法检测血清肿瘤坏死因子α(TNF-α)、血清肌钙蛋白T(cTnT)、心肌组织Toll样受体(TLR-4)水平;采用Western blot法检测肺组织TLR4、NF-κΒ蛋白表达水平;光学显微镜下观察心肌组织的病理变化。结果(1)术后6、12、24 h,CLP组、ES组血清TNF-α、cTnT及心肌组织TLR-4水平与Sham组相比明显升高(P<0.05);与CLP组相比,ES组血清TNF-α、cTnT及心肌组织TLR-4水平,在术后各时间点明显降低(P<0.05)。(2)Western blot结果显示,术后6、12、24 h,CLP组、ES组TLR4、NF-κΒ蛋白表达明显增高,与Sham组相比差异有统计学意义(P<0.05),且各时间点ES组TLR4、NF-κΒ蛋白表达均比CLP组明显降低(P<0.05)。(3)Sham组病理损伤最轻,CLP组病理损伤最重,ES组各时间点病理损伤均较CLP组明显减轻,较Sham组明显加重。(4)艾司洛尔能延长脓毒症大鼠生存时间,提高生存率。结论艾司洛尔能抑制炎症因子释放,减轻心肌损伤,延长脓毒症大鼠生存时间,其机制可能与抑制心肌TLR4、NF-κΒ的表达有关。Objective To explore early effects of short-actingβ1 receptor blocker esmolol on myocardial injury in septic rats.Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups(n=24 each),sham operation group(Sham),sepsis group(CLP)and esmolol group(ES).Six rats were randomly selected for each group to observe their survival time in seven days,and the remaining eighteen rats were randomly divided into three subgroups of 6 h,12 h and 24 h,with six rats in each subgroup.The Sham group was treated with cecal exploratory surgery while CLP and ES groups treated with cecal ligation and puncture to establish the sepsis model.Catheterization on the left internal jugular vein after the sepsis model was performed.Saline of 1 mL/h was continuously pumped into the Sham and CLP group by micropump for 6 h;esmolol dilution of 1 mL/h(15 mg/(kg·h))was continuously pumped into the ES group for 6 h.Rats in each subgroup were respectively executed at 6 h,12 h and 24 h after the operation.The plasma levels of TNF-α、cTnT and myocardial tissue TLR-4 were measured by ELISA.The expression levels of TLR4 and NF-κΒprotein in myocardial tissue were measured by Western blot.The pathological changes in myocardial tissues were observed with an optical microscope.Results(1)At 6 h,12 h and 24 h after cecal ligation and puncture,CLP and ES groups plasma levels of TNF-α、cTnT were significantly increased compared with the Sham group(P<0.05),and the plasma levels of TNF-α、cTnT in the ES group were significantly lower than the CLP group in each time point(P<0.05).At 6 h,12 h and 24 h after cecal ligation and puncture,myocardial tissue levels of TLR-4 in the CLP and ES groups were significantly increased compared with the Sham group(P<0.05),and ES group myocardial tissue levels of TLR-4 was also significantly lower than the CLP group in each time point(P<0.05).(2)At 6 h,12 h and 24 h after cecal ligation and puncture,Western blot showed that in the CLP and ES groups the expression of TLR4 and NF-κΒprotein in myocar

关 键 词：脓毒症 艾司洛尔 心肌损伤 肿瘤坏死因子Α 血清肌钙蛋白T 

分 类 号：R459.7[医药卫生—急诊医学]