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王清兵,路 超,于 刚.基于 TLR4 通路依托咪酯对感染性休克大鼠急性肺损伤的保护作用研究[J].中国比较医学杂志,2021,31(11):42~47.
基于 TLR4 通路依托咪酯对感染性休克大鼠急性肺损伤的保护作用研究
Protective effect of etomidate on acute lung injury in rats with septic shock via the TLR4 pathway
投稿时间:2020-10-22  
DOI:10. 3969 / j.issn.1671-7856. 2021. 11. 007
中文关键词:  感染性休克  急性肺损伤  依托咪酯  Toll 样受体 4  大鼠
英文关键词:septic shock  acute lung injury  etomidate  Toll-like receptor 4  rats
基金项目:
作者单位E-mail
王清兵 滨州市中心医院麻醉科,山东 滨州 251700 shentjk666@ 126.com 
路 超 滨州市中心医院产房,山东 滨州 251700  
于 刚 滨州市中心医院麻醉科,山东 滨州 251700  
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中文摘要:
       目的 探讨基于 Toll 样受体 4(TLR4)通路依托咪酯(Eto)对感染性休克大鼠急性肺损伤的保护作用。 方法 75 只大鼠随机分为假手术组、模型组、模型-脂多糖(LPS)组、模型-Eto 组、模型-Eto-LPS 组,各 15 只。除假手术组外,其余各组采用盲肠结扎穿孔法复制感染性休克大鼠模型,假手术组仅作剖腹手术。术前 30 min,模 型-LPS 组腹腔注射 LPS 15 mg / kg,模型-Eto 组腹腔注射依托咪酯 60 mg / kg,模型-Eto-LPS 组同时腹腔注射依托咪酯 60 mg / kg+LPS 15 mg / kg,模型组和假手术组腹腔注射生理盐水。检测术后 5 h 血清内毒素(ET)水平、BALF 中 IL-1β、IL-6、TNF-α,观察肺组织病理学改变,检测肺组织中 TLR4、髓样分化因子(MyD88)、核因子-κB p65(NF-κB p65)mRNA 和蛋白表达量。 结果 与假手术组比较,模型组、模型-LPS 组、模型-Eto 组、模型-Eto-LPS 组 ET 含量及 BALF 中 IL-1β、IL-6、TNF-α 水平均较高,其中模型-Eto 组<模型-Eto-LPS 组<模型组<模型-LPS 组(P<0. 05)。 HE 染色显示,模型组和模型-LPS 组肺泡明显充血,肺泡壁、肺间质增厚,大量炎性细胞浸润,且模型-LPS 组病变更为严重;模型-Eto 组和模型-Eto-LPS 组病变均减轻,偶有肺泡毛细血管充血和炎性细胞浸润,且模型-Eto 组减轻更为明显。与假手术组比较,模型组、模型-LPS 组、模型-Eto 组、模型-Eto-LPS 组肺组织中 TLR4、MyD88、NF-κB p65 mRNA 和蛋白相对表达量均较高,其中模型-Eto 组<模型-Eto-LPS 组<模型组<模型-LPS 组(P<0. 05)。 结论 Eto 对感染性休克大鼠急性肺损伤具有保护作用,可能通过抑制 TLR4 通路发挥调控作用。
英文摘要:
       Objective To investigate the protective effect of etomidate (Eto) mediated via the Toll-like receptor 4 (TLR4) pathway on acute lung injury in septic shock rats. Methods 75 rats were randomly divided into sham operation, model, model-lipopolysaccharide (LPS), model-Eto and model-Eto-LPS group with 15 rats in each group. Except for the sham operation group, the other groups underwent cecal ligation and perforation to establish the septic shock model. The sham operation group only underwent a laparotomy. 30 minutes before surgery, the model-LPS group was intraperitoneally injected with 15 mg / kg LPS, the model-Eto group was intraperitoneally injected with 60 mg / kg etomidate, and the model- Eto-LPS group was intraperitoneally injected with 60 mg / kg etomidate and 15 mg / kg LPS, model and sham operation groups were intraperitoneally injected with saline. The level of serum endotoxin (ET) and the levels of IL-1β, IL-6 and TNF-α in BALF were measured at 5 hours after the operation. Pathological changes were observed in lung tissue. mRNA and protein expression of TLR4, myeloid differentiation factor (MyD88), and nuclear factor-κB p65 (NF-κB p65) was detected in lung tissue. Results Compared with the sham operation group, ET contents and IL-1β, IL-6 and TNF-α levels in BALF were higher in the model, model-LPS, model-Eto and model-Eto-LPS groups, in the order of model-Eto grouP< model-Eto-LPS grouP<model grouP<model-LPS group (P<0. 05). HE staining showed that alveoli of model and model-LPS were obviously congested, the alveolar wall and lung interstitium had thickened, and a large number of inflammatory cells had infiltrated. The model-LPS group had more severe lesions. In model-Eto and model-Eto-LPS groups, the lesions were relieved with occasional alveolar capillary congestion, and inflammatory cell infiltration. The reductions were more obvious in the model-Eto group. Compared with the sham operation group, the relative expression of TLR4, MyD88 and NF-κB p65 mRNA and protein in lung tissues were higher in model, model-LPS, model-Eto and model-Eto-LPS groups in the order for model-Eto grouP<model-Eto-LPS grouP<model grouP<model-LPS group (P<0. 05). Conclusions Eto has a protective effect on acute lung injury in septic shock rats, which may play a regulatory role by inhibiting the TLR4 pathway.
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