长效重组链激酶(r-SK-PEG结合物)对大鼠急性肺栓塞动脉血气 、细胞因子的影响

目的 观察长效重组链激酶(r-SK-PEG结合物)对大鼠急性肺栓塞(PTE)动脉血气、肺动脉压和细胞因子的影响.方法 将160只SD雄性大鼠随机分为4组:假手术组(Ⅰ组)、肺栓塞组(Ⅱ组)、低分子肝素组(Ⅲ组)和长效重组链激酶组(Ⅳ组),每组各40只,采用自体血栓回输法建立PTE模型,造模成功后,Ⅰ组和Ⅱ组分别静脉滴注生理盐水,Ⅲ组皮下注射低分子肝素,Ⅳ组静脉点滴r-SK-PEG结合物,连续给药7 d,给药后1、3、6 h和1、3、5 d进行肺动脉压(mPAP)、右心室压力(RVP)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)及内皮素(ET-1)、基质金属蛋白酶-9(MMP-9)、一氧化氮(NO)测定.结果 Ⅳ组治疗后6h和1、3d的mPAP明显低于Ⅱ组(P<0.05),PaO2明显高于Ⅲ组(P<0.05);Ⅳ组治疗后6 h、1 d的mPAP明显低于Ⅲ组(P<0.05),RVP明显低于Ⅱ组、Ⅲ组(P<0.05);Ⅳ组治疗后6 h和1、3、5 d的PaO2明显高于Ⅱ组(P<0.05);Ⅳ组治疗后3、6 h的ET-1明显高于Ⅱ组、Ⅲ组(P<0.05);Ⅳ组治疗后1、3、5 d的MMP-9明显低于Ⅱ组(P<0.05);Ⅳ组治疗后3、6 h和1、3、5 d的NO明显高于Ⅱ组(P<0.05);Ⅳ组治疗后3、6 h的NO明显高于Ⅲ组(P<0.05).结论 PTE采用r-SK-PEG结合物治疗,能更加迅速缓解呼吸困难、纠正低氧血症、降低肺动脉压力和改善血管内皮功能.

The Effect of Long-acting Recombinant Streptokinase (r-SK-PEG Conjugates ) on the Arterial Blood Gas and Cytokines in Rats with Acute Pulmonary Embolism

Objective To investigate the effect of long-acting recombinant streptokinase ( r-SK-PEG conjugates) on the arterial blood gas , pulmonary artery pressure , and cytokines in rats with acute pulmonary embolism(PTE).Methods 160 male SD rats were divided randomly into four groups including the sham operation group (Group Ⅰ) ,pulmonary embolism group (Group Ⅱ) ,low molecular weight heparin group (Group Ⅲ) ,long-acting recombinant streptokinase group (Group Ⅳ) ,and each group consisted of 40 rats .The model of acute pulmonary embolism was established by the autologous thrombosis method .The model rats of Group Ⅰ and Ⅱ were treated with the intravenous infusion of normal saline , those of Group Ⅲ were given subcutaneously with low molecular weight heparin ,and those of Group Ⅳ were treated with the intravenous drip of long-acting recombinant streptokinase .The treatment lasted for 7 days in all the groups .The mean pressure of pulmonary artery (mPAP) , right ventricular pressure (RVP) ,arterial partial pressure of oxygen (PaO2 ) ,partial pressure of carbon dioxide (PaCO2 ) ,Endothelin-1 (ET-1) ,matrix metalloproteinase-9 (MMP-9) ,and nitric oxide (NO) were detected after being administered for 1h ,3h ,6h ,1d ,3d and 5d respectively .Results After being administered for 6h ,1d and 3d ,the mPAP level of Group Ⅳ was significantly lower than that of Group Ⅱ (P<0.05) and the PaO2 level of Group Ⅳ was significantly higher than that of Group Ⅲ (P<0.05) .After being administered for 6h and 1d ,the mPAP level of Group Ⅳ was significantly lower than that of Group Ⅲ ( P< 0.05 ) and the RVP level was significantly lower in Group Ⅳ than in Group Ⅱ and Ⅲ respectively (P<0.05) .After being treated for 6h ,1d ,3d and 5d ,the PaO2 level of Group IV was significantly higher than that of Group Ⅱ (P<0.05) .The ET-1 level was significantly higher in Group Ⅳ than in Group Ⅱ and Ⅲ respectively ( P< 0.05 ) . The level of MMP-9 was significantly lower in Group Ⅳ than in Group Ⅱ after being treated for 1d ,3d and 5d respectively (P<0.05) .The NO level of Group Ⅳ was significantly higher than that of Group Ⅱ after being treated for 3h ,6h ,1d ,3d and 5d respectively (P<0.05) and that of Group Ⅱ after being treated for 3h and 6h respectively .Conclusion The long-acting recombinant streptokinase (r-SK-PEG conjugates ) can alleviate the dyspnea more quickly , correct the hypoxemia ,reduce the pulmonary artery pressure and improve the vascular endothelial function in the treatment of acute pulmonary embolism .