艾司洛尔对脓毒症大鼠肺损伤及全身多器官炎症改善作用

Aserolol Improves Lung Injury and Multi-Organ Inflammation in Sepsis Rats

目的:探讨艾司洛尔(Esmolol, ES)对脓毒症大鼠肺损伤的保护以及全身多个器官炎症的改善作用。方法:60只清洁级SD雄性大鼠随机分为假手术(Sham)组、脓毒症(CLP)组和艾司洛尔(ES)组,每组20只。CLP、ES组采用盲肠结扎穿孔法制备脓毒症模型,Sham组仅开腹暴露盲肠后还纳腹腔。盲肠结扎穿孔术后1 h始,ES组每隔12小时经腹腔注射ES (20 mg/kg),其余两组在相同时间点给予等质量生理盐水。观察各组大鼠行为学及生存情况,术后48 h,酶联免疫吸附法(ELISA)检测血清及肺组织匀浆中炎性细胞因子水平,测定肺组织湿/干重(W/D)比值,苏木精–伊红(HE)染色观察脓毒症大鼠肺、心、肠组织形态学变化,免疫组化(IHC)染色检测肺组织中闭合蛋白(Occludin)、闭锁小带蛋白-1 (ZO-1)的表达。结果:艾司洛尔能有效提高脓毒症大鼠生存率。术后48 h,CLP组血清和肺组织匀浆中肿瘤坏死因子-α (TNF-α)、白细胞介素-10 (IL-10)均升高(P < 0.05),且ES组各因子含量显著低于CLP组(P < 0.05),48 h时,CLP组大鼠肺水肿明显,与CLP组相比,艾司洛尔可降低脓毒症大鼠肺水肿程度(P < 0.05)。48 h时,与Sham组相比,CLP组脓毒症大鼠肺、心、肠组织炎症细胞较Sham组明显浸润,ES组炎症细胞减少,细胞坏死程度较CLP组改善。术后48 h,与Sham组相比,CLP组脓毒症大鼠肺组织中Ocloudin和ZO-1的表达水平显著下降(P < 0.05)。与CLP组相比,ES组脓毒症大鼠肺组织中Occludin和ZO-1的表达水平升高(P < 0.05)。结论:艾司洛尔可通过减少炎性细胞因子释放,抑制机体炎症反应,保护脓毒症大鼠肺损伤并改善全身多个器官的炎症状态。

Objective: To investigate the effects of early application of Esmolol on lung injury and improvement of systemic inflammation of multiple organs in sepsis rats. Methods: Sixty male Sprague Dawley rats with seven or eight weeks were randomly divided into sham operation (Sham) group, sepsis (CLP) group and Esmolol (ES) group, with twenty rats in each group. Sepsis models were prepared by ce-cum ligation and perforation in the CLP and ES groups, while rats in Sham group only underwent laparotomy to expose the cecal. Starting from 1 h after cecal ligation puncture, the ES group was in-jected intraperitoneally with 20 mg/kg Esmolol every 12 h and the remaining two groups were in-jected with equal quality normal saline at the same time. We observe the behavioral changes of rats and survival rate in each group. The remaining surviving rats were sacrificed after 48 h surgery, every rat’s tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) levels were detected in rat blood and Lung tissue by enzyme linked immunosorbent assay (ELISA). The wet/dry-to- weight ratio of lung tissue of rats in each group was determined. The morphological changes of lung, heart and in-testine tissues in rats with sepsis were observed by hematoxylin-eosin staining. Immunohisto-chemical staining detected the expression of Occludin and ZO-1 in lung tissue. Results: Esmolol is effective in improving survival rate in rats with sepsis. At 48 h, compared with the Sham group, TNF-α and IL-10 were significantly increased in the CLP and ES groups (P < 0.05) and the content of each factor in the ES group was significantly lower than in the CLP group (P < 0.05). At 48 h, pulmo-nary edema in rats in the CLP group was obvious, and compared with the CLP group, esmolol could reduce the degree of pulmonary edema in rats with sepsis (P < 0.05). At 48 h, compared with the Sham group, the inflammatory cells of lung, heart and intestinal tissues of rats with sepsis in the CLP group were infiltrated significantly compared with the Sham group, while the inflammatory cells in the ES group were reduced and the degree of cell necrosis improved compared with the CLP group. At 48 h after surgery, compared with the Sham group, the expression levels of Occludin and ZO-1 in the lung tissue of rats with sepsis in the CLP group decreased signi- ficantly (P < 0.05). Compared with the CLP group, the expression levels of Occludin and ZO-1 in the lung tissue of sepsis rats in the ES group increased (P < 0.05). Conclusion: Esmolol exerts a protec- tive effect against lung injury and the inflammatory state of multiple organs throughout the body in sepsis rats by inhibiting inflammatory cytokine release.