黄连素在铜绿假单胞菌致大鼠肺炎中的抗炎作用

Anti-inflammatory effects of berberine in Pseudomonas aeruginosa induced pneumonia in rats

  • 摘要: 目的 本研究旨在探讨黄连素对铜绿假单胞菌所致大鼠肺炎模型的炎症及NF-κB信号通路活性的影响。方法 将40只健康成年雄性大鼠随机分为对照组、黄连素组、模型组及黄连素+模型组,每组10只。使用气管注射铜绿假单胞菌建立大鼠肺炎模型,对照组给予等量生理盐水,黄连素+模型组于模型建立后2 h灌胃给予黄连素(200 mg/kg),黄连素组给予等量生理盐水2 h后给予黄连素(200 mg/kg)。观察实验动物48 h处死动物,计数支气管肺泡灌洗液(BALF)中的白细胞,酶联免疫吸附法(ELISA)检测BALF中NF-κB信号转导下游炎症介质TNF-α与IL-6的水平,测定肺组织的髓过氧化物酶(MPO)活性,并使用蛋白印迹法(Western blotting)对肺组织中的NF-κB信号传导通路相关蛋白包括NF-κB p65、p-NF-κB p65、IκBα及p-IκBα的蛋白水平进行测定;结果 与对照组相比,铜绿假单胞菌致大鼠肺炎可明显增加BALF中的白细胞数量(P<0.001),促进BALF中炎症因子TNF-α与IL-6的产生(P<0.001),增强MPO活性(P<0.001),此外还促进了NF-κB信号传导通路的活化(P<0.001)。给予黄连素治疗可逆转上述变化。结论 本研究发现黄连素对铜绿假单胞菌诱导的大鼠肺炎有保护作用,对铜绿假单胞菌诱导炎症反应的改善作用可能与抑制NF-κB信号通路活化有关。

     

    Abstract: OBJECTIVE To investigate the effects of berberine on the inflammation and the activation of NF-κB signal pathway in a rat model of Pseudomonas aeruginosa induced pneumonia. METHODS Total of 40 healthy adult male rats were randomly divided into 4 groups(n=10): the control group, berb group, model group and berb+model group. P.aeruginosa was injected into the lung trachea to establish the pneumonia model in rats. The control group was given the same amount of normal saline. The berb+model group was given berberine(200 mg/kg) by oral administration 2 hours after the model was established. The berb group was given berberine(200 mg/kg) 2 hours after the same amount of normal saline was given. The white cells in bronchoalveolar lavage fluid(BALF) were counted and the levels of cytokines including TNF-α and IL-6 in the downstream of NF-κB signal pathway in BALF were measured by enzyme-linked immunosorbent assay(ELISA). Myeloperoxidase(MPO) activity in lung tissue was measured, and the protein levels of NF-κ B signaling including NF-κB p65, p-NF-κB p65, IκBα and p-IκBα were measured. RESULTS Compared with the control group, P.aeruginosa induced pneumonia in rats significantly increased the number of white cells in BALF(P<0.001), which significatly increased the production of inflammatory factors such as TNF-α and IL-6 in BALF(P<0.001), up-regulated MPO activity(P<0.001), and also promoted the activation of NF-κB signaling pathway(P<0.001). On the contrary, berberine could reverse these change. CONCLUSION The findings suggested a therapeutic potential of berberine on P.aeruginosa induced pneumonia. The ameliorative effects on the P.aeruginosa induced inflammation might be associated with the inhibition of activation of the NF-κB signaling pathway.

     

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