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目的:探讨苦参对大鼠慢性铜绿假单胞菌(PA)生物膜肺炎模型的影响。方法:由支气管内直接注入PA(菌种为PAO579)藻酸盐微粒(1×109CFU.mL-1),建立慢性PA生物膜感染模型,并于术后第2天开始给予3种不同剂量的苦参煎剂(3,6,12g·kg-1)或灭菌生理盐水(NS)灌胃治疗,每天1次,连续治疗14d,2周后评估各组的肺组织病理学、血清PA特异性抗体IgG水平、肺部细胞因子IFN-γ反应的变化及KB纸片琼脂扩散试验。结果:PA感染2周后,3种剂量的苦参组均可明显减轻PA感染大鼠肺部大体观病变和降低肺脓肿发生率(P<0.001);镜下观察发现苦参各治疗组主要表现为慢性炎症(以单个核细胞浸润为主),苦参中、高剂量组有急性炎症(以多形核白细胞浸润为主)的动物数明显低于模型组(P<0.05);免疫学指标检测发现苦参中、高剂量组能够显著下调血清PA特异性IgG抗体(P<0.05或P<0.001),且血清IgG水平与苦参剂量呈显著负相关(r=-0.95,P<0.01);苦参各治疗组的肺部IFN-γ水平显著高于模型组(P<0.01),尤其是苦参高剂量组较模型组高10倍之多(P<0.001)。同时,苦参各治疗组IFN-γ水平与苦参剂量呈正相关关系(r=0.9,P<0.02)。另外,KB纸片琼脂扩散法检测发现苦参具有较弱的抗PA活性,而生理盐水无抗PA活性。结论:苦参可能通过调控感染机体的免疫反应,诱导Th1型反应,从而对PA肺感染动物有多方面的治疗作用,而12g·kg-1的苦参是本研究的最佳剂量。
Objective: To investigate the effect of Sophora flavescens on the model of chronic Pseudomonas aeruginosa (PA) biofilm pneumonia in rats. Methods: PA (bacterial strain PAO579) alginate particles (1 × 109CFU.mL-1) were directly injected into the bronchial tube to establish chronic PA biofilm infection model. Three different doses of Kushen decoction (3, 6, 12 g · kg-1) or sterile saline (NS) were intragastrically administered once a day for 14 days and 2 weeks respectively. The lung histopathology, serum specific PA IgG antibody levels in serum, changes in cytokine IFN-γ in lungs and KB disk diffusion test. Results: After 2 weeks of PA infection, the three doses of Sophora flavescens group could significantly reduce the lung gross lesion and reduce the incidence of pulmonary abscess in PA-infected rats (P <0.001). Microscopically, Chronic inflammation (infiltrated by mononuclear cells) was the main cause of acute inflammation (infiltration of polymorphonuclear leukocytes) in the medium and high dose Sophora flavescens group (P <0.05). Immunology The index test found that the medium and high dose of Sophora flavescens can significantly reduce serum PA specific IgG antibody (P <0.05 or P <0.001), and the level of IgG in serum was negatively correlated with the dose of Sophora flavescens (r = -0.95, P <0.01 ). The levels of IFN-γ in the lungs of each treatment group were significantly higher than those in the untreated group (P <0.01), especially in the high-dose Sophora flavescens group than in the model group (P <0.001). At the same time, the level of IFN-γin each treatment group was positively correlated with the dose of Sophora flavescens (r = 0.9, P <0.02). In addition, KB paper agar diffusion test found that Sophora flavescens has a weak anti-PA activity, while the saline did not have anti-PA activity. Conclusion: Sophora flavescens may induce Th1-type response by regulating the immune response of the infected organism, which may have many therapeutic effects on PA-infected animals. Sophora flavescens 12g · kg-1 is the optimal dose for this study.