胸腔内注入尿激酶对实验性结核性胸膜炎的影响  

The effects of intrapleural urokinase on tuberculous pleurisy in rat model

作　　者：何桥[1] 谢灿茂[2] 谭守勇[1] 林丽白[3] 邓晓华[1] 易小萍[1] 蔡杏珊[1] 许蕴怡[1] 刘燕[1] 

机构地区：[1]广州市胸科医院,广州510095 [2]中山大学第一附属医院,广州510080 [3]广州医学院预防医学教研室,广州510170

出　　处：《中国防痨杂志》2007年第6期517-522,共6页Chinese Journal of Antituberculosis

基　　金：广东省医学科研基金(A2001587)

摘　　要：目的观察胸腔内注入尿激酶对结核性胸膜炎的炎症反应的影响。方法用标准人型结核分枝杆菌菌株H37RV0.03 mg/只注入90只Wistar大鼠胸腔内,24 h后随机分成2组。实验组:胸腔内注入尿激酶600 U/(ml.只);对照组:胸内注入生理盐水1 ml/只。在注入后8 h2、4 h3、2 h4、8 h、3 d、5 d、7 d、10 d和15 d分别处死动物,每次每组各5只。解剖胸腔,记录胸腔积液量,观察胸腔、胸膜大体及镜下病理改变。检测胸腔积液中白细胞计数(WBC)及分类、总蛋白(TP)、葡萄糖(GLU)和乳酸脱氢酶(LDH)的含量;测定可溶性细胞间粘附分子-1(sICAM-1)、转化生长因子-β1(TGF-β1)和γ干扰素(IFN-γ)的水平;同时测定外周血的凝血酶原时间(PT)、凝血酶时间(TT)和部分活化凝血酶原时间(APTT);测量胸膜厚度并对胸膜、肺组织作病理学观察。结果实验组第1 d和2 d胸腔积液量[(6.1±0.6)ml和(7.0±0.2)ml]明显多于对照组[(5.4±0.5)mml和(5.2±0.2)ml],第7 d和10d则明显低于对照组[(2.4±0.4)ml和(0.3±0.1)mlVS(5.2±0.5)ml和(3.3±0.6)ml,P<0.01]。实验组胸腔积液的WBC在初期(8 h)和48 h后均明显低于对照组(P<0.01),中性粒细胞百分率也明显低于对照组(P<0.01)。实验组炎症标志物LDH在8 h2、4 h、32 h内明显低于对照组[(15.5±0.7、16.1±1.2、17.5±1.4VS18.0±0.9、18.4±0.6、18.5±1.2)μmol/(s.L),P<0.01]。实验组胸腔积液sICAM-1水平在整个观察期均明显低于对照组(P<0.01),而TGF-β1仅在第5 d和7 d低于对照组[(29.4±3.3、22.7±3.4VS45.6±3.2、45.2±2.7)ng/ml,P<0.01];IFN-γ在第7 d也明显低于对照组[(151.6±21.4VS178.2±18.6)pg/ml,P<0.01]。IFN-γ/TGF-β1在第3 d后明显高于对照组,第7 d最高(6.74±0.9VS3.15±1.8,P<0.01)。同时还观察到实验组胸腔内粘连带的形成时间较迟而且数量也较少,胸膜厚度较薄(P<0.01)。外周血凝血功能与对照组比较无显著性差异。结论胸腔内注入尿激酶可使结核性胸膜炎早期胸液产生较多而Objective To observe the effects of intrapleural urokinase on the inflammatory reaction of tuberculous pleurisy.Method Ninety Wistar rats were intrapleurally injected with 0.03mg of Mycobacterium tuberculsis standard strain H37RV,respectively.At 24 hours later,the rats were randomized into two groups:the urokinase group(UKG): 600U/ml of urokinase was intrapleurally injected in each rat.the control group(CG): 1ml of saline was intrapleurally injected in each rat.The rats were killed in batch at 8 hours,24 hours,32 hours,2 days,3 days,5 days,7 days and 10 days after the second injection.5 rats were killed each time.Then the thoraxes were opened and the amount of pleural effusion was recorded,gross pathology of thoracic cavity and histopathology of pleural tissues were observed.The white blood cell(WBC) count and differentials,levels of total protein(TP),glucose(Glu) and lactic dehydrogenase(LDH) in pleural effusions were determined.Pleural fluid was analyzed for the levels of soluble intercellular adhesion molecule-1(sICAM-1),transforming growth factor β1(TGF-β1) and interferon γ(IFN-γ).The prothrombin time(PT),thrombin time(TT) and activated partial thromboplastin time(APTT) of peripheral blood were simultaneously determined.The thickness of pleura was measured and the pathology of pleural and lung tissues was observed. Results The amount of pleural effusions on days 1 and 2 was significantly greater in the UKG than in the CG [(6.1±0.6、7.0±0.2) vs(5.4±0.5、5.2±0.2)ml](P< 0.01).While on days 7 and 10 the amount of effusions was significantly lower in the UKG than in the CG[(2.4±0.4,0.3±0.1vs5.2±0.5,3.3±0.6)ml](P<0.01).The WBC in the UKG were lower at 8 hours and after 48 hours than those in the CG,as well as the neutrophil percentage(P<0.01).The level of inflammatory marker LDH at hours 8,24 and 32 was significantly lower in the UKG than that in the CG[(15.5±0.7,16.1±1.2,17.5±1.4 vs18.0±0.9,18.4±0.6,18.5±1.2)μmol·s-1·L-1,P<0.01].During the whole observation period,the level of sICAM-1 in ple

关 键 词：结核 胸膜/药物疗法 尿纤溶酶原激活物 

分 类 号：R521.7[医药卫生—内科学]