[关键词]
[摘要]
目的 探究灵芝多糖对盲肠结扎穿孔导致的脓毒症急性肺损伤大鼠肺功能及肺组织炎症的影响。方法 SD大鼠随机分成对照组、模型组及灵芝多糖低、中、高剂量(50、100、200 mg/kg)组和乌司他丁组,除对照组外,其余各组大鼠均采用盲肠结扎穿孔法制备脓毒症模型。给予灵芝多糖和乌司他丁进行干预,采用全自动血气分析仪检测大鼠O2分压[p(O2)]和CO2分压[p(CO2)];取大鼠右肺中叶计算肺组织湿/干质量;采用ELISA法检测大鼠肺泡灌洗液中白细胞介素-6(interleukin-6,IL-6)、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和核因子-κB(nuclear factor-κB,NF-κB)水平;采用苏木素-伊红(HE)染色法检测大鼠肺组织病理变化;采用Western blotting法检测大鼠肺脏组织中Toll样受体4(toll like receptor 4,TLR4)、p65、磷酸化p65(p-p65)蛋白表达水平。结果 与对照组比较,模型组大鼠肺组织结构破坏,肺泡间隔明显增厚,有大量炎性细胞浸润,肺组织炎症评分显著升高(P<0.05);肺组织湿质量/干质量显著升高(P<0.05);p(CO2)显著升高(P<0.05),p(O2)显著降低(P<0.05);肺泡灌洗液中IL-6、IL-1β、TNF-α和NF-κB水平均显著升高(P<0.05);肺组织TLR4和p-p65/p65蛋白表达水平显著升高(P<0.05)。与模型组比较,灵芝多糖组大鼠肺组织损伤减轻,肺泡完整性较好,炎症细胞浸润减少,肺组织炎症评分显著降低(P<0.05);肺组织湿质量/干质量显著降低(P<0.05);p(CO2)显著降低(P<0.05),p(O2)显著升高(P<0.05);肺泡灌洗液中IL-6、IL-1β、TNF-α和NF-κB水平均显著降低(P<0.05);肺组织TLR4和p-p65/p65蛋白表达水平显著降低(P<0.05),呈剂量相关性。结论 灵芝多糖能够通过抑制TLR4/NF-κB信号通路,从而减轻脓毒症大鼠炎症反应并保护肺功能。
[Key word]
[Abstract]
Objective To explore the effect of Ganoderma lucidum polysaccharides (GLP) on lung function and lung tissue inflammation in rats with septic acute lung injury caused by cecal ligation and perforation. Methods SD rats were randomly divided into control group, model group, low-, medium-, high-dose (50, 100, 200 mg/kg) GLP groups and ulinastatin group. Except for rats in control group, rats in the other groups were used to establish sepsis model by cecal ligation and perforation method. GLP and ulinastatin were given to intervene, and p(O2) and p(CO2) of rats were detected by automatic blood gas analyzer; Middle lobe of the right lung of rats was taken to calculate the wet/dry weight of lung tissue; Levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in alveolar lavage fluid of rats were detected by ELISA; Hematoxylin-eosin (HE) staining was used to detect pathological changes in rat lung tissue; Western blotting was used to detect expressions of toll like receptor 4 (TLR4), p65, and phosphorylated p65 (p-p65) in lung tissue of rats. Results Compared with control group, lung tissue structure of rats in model group was destroyed, the alveolar compartment was significantly thickened, with a large number of inflammatory cells infiltration, and the lung tissue inflammation score was significantly increased (P < 0.05); Wet/dry weight of lung tissue was significantly increased (P < 0.05); p(CO2) was significantly increased (P < 0.05), p(O2) was significantly decreased (P < 0.05); IL-6, IL-1β, TNF-α and NF-κB levels in alveolar lavage fluid were significantly increased (P < 0.05); Expressions of TLR4 and p-p65/p65 in lung tissue were significantly increased (P < 0.05). Compared with model group, lung tissue damage of rats in GLP group was reduced, alveolar integrity was improved, inflammatory cell infiltration was reduced, lung inflammation scores was significantly reduced (P < 0.05); Wet/dry weight of lung tissue was significantly reduced (P < 0.05); p(CO2) was significantly reduced (P < 0.05), p(O2) was significantly increased (P < 0.05); IL-6, IL-1β, TNF-α and NF-κB levels in alveolar lavage fluid were significant decreased (P < 0.05); Expressions of TLR4 and p-p65/p65 in lung tissue were significantly reduced (P < 0.05), in a dose-dependent manner. Conclusion GLP can inhibit TLR4/NF-κB signaling pathway, thereby reducing the inflammatory response in septic rats and protecting lung function.
[中图分类号]
R285.5
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