β_1受体阻滞剂上调肠道上皮细胞HO-1对脓毒症大鼠肠道功能的保护作用  

Protective Effects of β_1 Blocker on Intestinal Injury in Septic Rats Correlated with Heme Oxygenase-1 Up-regulation

作　　者：彭相虹 蒋磊[1] 龚睿[1] 于未 赵鸣雁[1] 

机构地区：[1]哈尔滨医科大学附属第一医院重症医学科,150001

出　　处：《医学研究杂志》2016年第9期63-66,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81171785)

摘　　要：目的探讨β1受体阻滞剂艾司洛尔(Esmolol)能否上调血红素氧合酶-1(heme oxygenase-1,HO-1)起到对脓毒症大鼠肠道功能的保护作用。方法本实验于哈尔滨医科大学附属第一医院外科中心实验室完成。40只雄性Wistar大鼠按随机数字表法分为4组:假手术组(sham组,n=10)、脓毒症组(CLP组,n=10)、艾司洛尔干预组(Esmolol+CLP组,n=10)、HO-1抑制剂组(Esmolol+Zn PP+CLP组,n=10)。采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型,Esmolol组通过静脉输注艾司洛尔注射液,速度为15mg/(kg·h),Esmolol+Zn PP+CLP组术前1h腹腔内注射Zn PP溶液(40μmol/kg),术后同速静脉输注艾司洛尔注射液。其余各组大鼠腹腔注射等体积生理盐水,并且静脉输注等渗盐水,速度2ml/(kg·h)。术后12h处死大鼠,ELISA法检测各组血清肿瘤坏死因子(TNF-α)和白细胞介素(IL-1β)水平,采用蛋白印迹法及免疫组化法检测大鼠肠组织HO-1表达水平,光学显微镜观察大鼠肠组织病理变化情况。结果与Sham组相比,CLP组大鼠血清TNF-α、IL-1β水平均明显升高(43.71±6.24pg/ml vs 2742.69±221.71pg/ml,52.69±14.15pg/ml vs 482.73±125.49pg/ml,P<0.05);肠组织中HO-1水平表达升高(P<0.05);肠组织病理损伤明显。与CLP组相比,Esmolol+CLP组血清TNF-α、IL-1β水平均明显下降(2742.69±221.71pg/ml vs 968.81±99.46pg/ml,482.73±125.49pg/ml vs 156.15±38.29pg/ml,P<0.05);肠组织HO-1水平表达明显升高(P<0.05);肠组织病理损伤程度减轻。与CLP组相比,Esmolol+Zn PP+CLP组大鼠血清TNF-α、IL-1β水平无明显差异(2742.69±221.71pg/ml vs 2545.18±173.74pg/ml,482.73±125.49pg/ml vs 474.43±113.98pg/ml,P>0.05);肠组织病理损伤程度无明显差异。结论 Esmolol能改善脓毒症诱发的肠道损伤,其可能是通过上调HO-1通路来减轻肠组织炎性反应,继而减轻肠道损伤。Objective To investigate the effects of Esmolol on intestinal injury and its association with heine oxygenase - 1 in rats with sepsis. Methods Forty male Wistar rats were randomly divided into four groups： Sham group （ n = 10） , CLP group （ n = 10） , Es- molol ＋ CLP group （n = 10） and Esmolol ＋ ZnPP ＋ CLP group （n = 10）. Cecal ligation and puncture （CLP） was imployed to in- duce septic intestinal injury. Rats in Esmolol group received intravenous esmolol infusion [ 15mg/（kg · h） ] for 12 hours. Rats in Esmolol ＋ ZuPP ＋ CLP group received intraperitoneal injection with ZnPP solution （40μmol/kg） 1 hour before CLP procedures and intrave- nous esmolol infusion [ 15mg/（ kg· h） ] for 12 hours after CLP procedures. Rats in the other groups were intraperitoneally injected with the same volume of saline and received intravenous infusion of isotonic saline [ 2ml/（kg ~ h） ]. The rats were sacrificed after 12 hours. ELISA assay was used to test serum TNF - α and IL - 1β level. Western blot and immuuohistochemical staining were used to determine the expression of HO - 1 in intestinal tissue. The pathological changes of intestinal tissue were evaluated under optical microscope. One - way analysis of variance （ANOVA） was used for comparisons among the groups, and Tukey＇s test was performed for further comparison, and difference was statistically significant at P 〈 0.05. Results Compared with the Sham group, serum TNF -α, IL - 1β levels were both significantly higher （43.71 ± 6.24pg/ml vs 2742.69 ± 221.7 lpg/ml, 52.69 ± 14.15pg/ml vs 482.73 ± 125.4pg/ml, P 〈 0.05 ） , HO - 1 protein expression in intestinal tissue were slightly increased （P 〈 0.05 ） , and the intestinal histopathologieal damage was obivi- ously aggravated in the CLP group. Compared with CLP group, serum TNF - α, IL - 1β levels were both significantly decreased （2742.69 ± 221.71pg/ml vs 968.81± 99.46pg/ml, 482.73 ± 125.49pg/ml vs 156.15 ± 38.29pg/ml, P 〈 0.05 ）, the intestin

关 键 词：Β1-受体阻滞剂 脓毒症 血红素氧合酶-1 肠道损伤 

分 类 号：R965[医药卫生—药理学]