β1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
投稿时间:2016-02-16  修订日期:2016-03-02  点此下载全文
引用本文:彭相虹,蒋磊,龚睿,于未,赵鸣雁.β1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[J].医学研究杂志,2016,45(9):63-66
DOI: 10.11969/j.issn.1673-548X.2016.09.017
摘要点击次数: 1103
全文下载次数: 751
作者单位E-mail
彭相虹 150001 哈尔滨医科大学附属第一医院重症医学科  
蒋磊 150001 哈尔滨医科大学附属第一医院重症医学科  
龚睿 150001 哈尔滨医科大学附属第一医院重症医学科  
于未 150001 哈尔滨医科大学附属第一医院重症医学科  
赵鸣雁 150001 哈尔滨医科大学附属第一医院重症医学科 mingyan1970@126.com 
基金项目:国家自然科学基金资助项目(81171785)
中文摘要: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+ZnPP+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+ZnPP+CLP组术前1h腹腔内注射ZnPP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+ZnPP+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。
中文关键词:β1-受体阻滞剂  脓毒症  血红素氧合酶-1  肠道损伤
 
Protective Effects of β1 Blocker on Intestinal Injury in Septic Rats Correlated with Heme Oxygenase-1 Up-regulation
Abstract:Objective To investigate the effects of Esmolol on intestinal injury and its association with heme 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), Esmolol+CLP group (n=10) and Esmolol+ZnPP+CLP group (n=10). Cecal ligation and puncture (CLP) was imployed to induce septic intestinal injury. Rats in Esmolol group received intravenous esmolol infusion [15mg/(kg·h)] for 12 hours. Rats in Esmolol+ZnPP+CLP group received intraperitoneal injection with ZnPP solution (40μmol/kg) 1 hour before CLP procedures and intravenous 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 immunohistochemical 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±221.71pg/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 histopathological damage was obiviously 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 intestinal tissue levels of HO-1 protein expression were significantly increased (P<0.05), and the intestinal pathological injury was mitigated in the Esmolol+CLP group. Compared with CLP group,serum TNF-α, IL-1β levels had no obvious difference(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),and the intestinal pathological injury had no obvious difference in Esmolol+ZnPP+CLP group. Conclusion Esmolol relieves the intestinal inflammation and improves sepsis-induced intestinal damage, which may be correlated with HO-1 up-regulation.
keywords:β1-receptor blocker  Sepsis  Heme oxygenase-1  Intestinal injury
查看全文  查看/发表评论  下载PDF阅读器

京公网安备 11010502037822号