中国中药杂志

2010, v.35(03) 352-355

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苦参煎剂对大鼠慢性铜绿假单胞菌生物膜肺部感染模型的影响
Effects of Sophora flavescens on rat model of chronic Pseudomonas aeruginosa biofilm pneumonia

郭向华;郭润华;宋志军;
GUO Xianghua1,GUO Runhua2,SONG Zhijun3 (1. Department of Pathophysiology,Guangdong Medical Colledge,Dongguan 523808,China; 2. 411 General Hospital of PLA,Shanghai 200083,China; 3. Department of Clinical Microbiology,University Hospital of Copenhagen,Denmark DK-2100)

摘要(Abstract):

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 study the therapeutical effects of the Chinese medicinal herb,Sophora flavescens (SFA) on a rat model of chronic Pseudomonas aeruginosa(PA)biofilm pneumonia. Method:Rats were challenged intratracheally with alginate embedded PA strain PAO579 at the concentration of 1×109 colony-forming units per milliliter (CFU·mL-1). After challeng on the second day,three different doses SFA or sterile normal saline (NS) were administered by gastric intubation once a day for two weeks. Two weeks post intratracheal challenge with P. aeruginosa,parameters were evaluated. Result:Two weeks after challenge,a remarkable serum antibody response and significant infiltration of numerous polymorphonuclear leukocytes (PMN) with lower IFN-γ production in the lungs were found in the model group. However,milder macroscopic and lower incidence of lung abscesses were found in all the three groups received different doses of SFA treatment compared to the model group (P<0.001). Meanwhile,the microscopic lung pathology in all SFA-treated groups were characterized by chronic inflammation dominated by mononuclear leukocytes(MN).The rat number with acute inflammation in group II,III was significantly lower than that in the model group(P<0.05). Furthermore,the serum level of anti-PA IgG was down-regulated in group II and III (P<0.05 or P<0.001),and serum IgG level was negatively correlated with the SFA doses (r=-0.95,P<0.01). In all the SFA-treated groups higher IFN-γ production in the lung was found compared to the model group (P<0.001) ,and the lung IFN-γ level was positively correlated with the SFA doses (r=0.9,P<0.02). These findings indicate that SFA has an effect on inducing Th1 type of immune response. The anti-PA activity test of SFA was weakly positive whereas NS was negative. Conclusion:SFA treatment significantly reduced pathology,which might be associated with a shift of local immune responding type from a Th2 like to Th1 like that might provide a better protection to the rats with chronic P. aeruginosa lung infection. And these results also showed that the SFA dose of 12 g·kg-1 was the best dosage in this present study.

关键词(KeyWords): 苦参;铜绿假单胞菌;细菌生物膜
Sophora flavescens; Pseudomonas aeruginosa; bacterial biofilm

Abstract:

Keywords:

基金项目(Foundation): 湛江市科技攻关项目(2007C05012)

作者(Authors): 郭向华;郭润华;宋志军;
GUO Xianghua1,GUO Runhua2,SONG Zhijun3 (1. Department of Pathophysiology,Guangdong Medical Colledge,Dongguan 523808,China; 2. 411 General Hospital of PLA,Shanghai 200083,China; 3. Department of Clinical Microbiology,University Hospital of Copenhagen,Denmark DK-2100)

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