Abstract: 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 H₃₇R_V,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 pleural effusion was significantly lower in the UKG than in the CG(P＜0.01),while the TGF-β₁ was lower merely on the days 5 and 7 [(29.4±3.3,22.7±3.4 vs 45.8±7.7,45.2±6.4)ng/ml,P＜0.01].IFN-γ was lower in the UKG than CG only on day 7 [(151.6±21.4 vs178.2±18.6)pg/ml,P＜0.01].On days 3 later,IFN-γ/TGF-β₁ in the UKG was significantly higher than that in the CG and reached the highest level on Day 7(6.74±0.9 vs3.15±1.8,P＜ 0.01).The formation of adhesion was slower and the extent of adhesion was lesser in the UKG than those in the CG,with less thickening of pleura was observed in the UKG(P＜0.01).No significant difference in coagulation time of peripheral blood was found between the two groups.Conclusions Intrapleural urokinase could lead to more pleural effusion and subsequent faster pleural fluid absorption in tuberculous pleurisy.The inflammatory reaction in thoracic cavity could be relieved by intrapleural urokinase,and thus the adhesion and thickening of pleura could be reduced.It suggests that intrapleural urokinase is effective in the treatment of tuberculous pleurisy.

Key words: Tuberculosis pleural/drug therapy, Urinary plasminogem activator