乌司他丁通过抑制ERK信号通路减轻大鼠脓毒症性肺损伤

发布时间：2018-10-05 20:36

【摘要】：目的探讨乌司他丁(UTI)对脓毒症性急性呼吸窘迫综合征(ARDS)大鼠的肺保护作用及可能机制。方法 24只Wistar大鼠按随机数字表法分为对照组、模型组(LPS组)、乌司他丁组(UTI组)每组8只。采用腹腔注射脂多糖(LPS)(10 mg/kg)的方法制备大鼠ARDS模型,乌司他丁组在左侧腹腔注射LPS后1 h后在右侧腹腔注射乌司他丁20 000 U/kg,对照组注射同等剂量的生理盐水,各组大鼠留取肺组织及血浆标本。计算肺组织湿/干质量(W/D);光镜下观察肺组织病理改变;用ELISA法检测各组血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-18(IL-18)、肺表面活性物质A(SPA)含量;免疫组化法检测细胞外信号调节蛋白激酶(ERK)蛋白表达情况,Western blot法检测肺组织中磷酸化ERK(p ERK)蛋白表达的变化。结果光镜下观察对照组肺组织结构完整,肺泡腔清晰;LPS组肺泡壁增厚,渗出明显,肺组织出现损伤性变化;UTI组病理改变较LPS组明显减轻。与对照组比较,LPS组肺组织W/D增加,而血浆TNF-α、IL-18、SPA含量均明显升高(P0.05);与LPS组比较,UTI组肺组织W/D减少,而血浆TNF-α、IL-18、SPA含量含量均明显降低,差异有统计学意义;免疫组化结果显示:与对照组比较,LPS组ERK蛋白在胞浆和胞核表达均明显增加,而UTI组较LPS组表达均明显减少;Western blot检测结果显示:与对照组比较,LPS组肺组织ERK蛋白表达均明显增高,而UTI干预组蛋白表达均明显受抑制。结论乌司他丁通过抑制ERK信号通路减轻炎症反应及肺表面活性物质量及活性,发挥对LPS致大鼠脓毒性ARDS的保护作用。
[Abstract]:Objective to investigate the lung protective effect and possible mechanism of ulinastatin (UTI) on septic acute respiratory distress syndrome (ARDS) rats. Methods Twenty-four Wistar rats were randomly divided into control group (LPS group) and ulinastatin group (UTI group). The rat model of ARDS was established by intraperitoneal injection of lipopolysaccharide (LPS) () for 10 mg/kg. Ulinastatin was injected into the right side of the rat intraperitoneally 1 hour after LPS injection on the left side, and the control group was injected with the same dose of normal saline. Lung tissue and plasma samples were collected from rats in each group. Lung wet / dry weight (W / D) was calculated, pathological changes of lung tissue were observed under light microscope, plasma levels of tumor necrosis factor- 伪 (TNF- 伪), interleukin-18 (IL-18) and pulmonary surfactant (A (SPA) were detected by ELISA assay. The expression of extracellular signal-regulated protein kinase (ERK) protein was detected by immunohistochemistry and the expression of phosphorylated ERK (p ERK) protein was detected by Western blot method. Results under the light microscope, the lung structure of the control group was intact, and the alveolar wall was thickened and exudated obviously in the control group. The pathological changes of the lung tissue in the UTI group were significantly less than those in the LPS group. Compared with the control group, the lung tissue W- / D increased, while the plasma TNF- 伪 -IL-18 SPA increased significantly (P0.05), compared with the LPS group, the lung tissue W- / D decreased, and the plasma TNF- 伪-IL-18- SPA decreased significantly (P < 0.05). The results of immunohistochemistry showed that the expression of ERK protein in cytoplasm and nucleus was significantly increased in lipopolysaccharide group compared with the control group. The expression of ERK in UTI group was significantly lower than that in LPS group. The results showed that compared with control group, the expression of ERK protein in UTI group was significantly higher than that in LPS group, while the expression of ERK protein in UTI intervention group was significantly inhibited. Conclusion Ulinastatin can attenuate the inflammatory reaction and the quality and activity of pulmonary surfactant by inhibiting ERK signaling pathway, and play a protective role on septic ARDS induced by LPS in rats.
【作者单位】：内蒙古医科大学附属医院重症医学科;内蒙古自治区人民医院神经内科;
【基金】：内蒙古自治区自然基金项目(2013MS1128) 内蒙古自治区卫生与计划生育委员会基金(201302077)
【分类号】：R459.7

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