辛伐他汀对大鼠急性肺栓塞的保护作用

目的探讨辛伐他汀对大鼠急性肺栓塞的保护作用及其机制。方法将72只Sprague-Dawley大鼠随机分为假手术组，肺栓塞模型组和辛伐他汀干预组，每组24只。在造模后2h，6h，24h分别测定各组大鼠的右心室收缩压（RVSP）和平均肺动脉压（mPAP），分离肺脏进行HE染色及肺脏病理学检查。在造模后6h测定各组大鼠的动脉血气和肺血管内皮型一氧化氮合酶（eNOS）蛋白表达。应用ELISA法测定各组大鼠血浆白介素-6（IL-6）和肿瘤坏死因子Ⅱ（TNF-α）水平。结果肺栓塞模型组大鼠不同时间点的mPAP,RVSP均较假手术组明显升高（P〈0．01）。辛伐他汀干预组大鼠不同时间点的mPAP、RVSP与肺栓塞模型组比较均显著降低（P〈0．05）。肺栓塞模型组大鼠6h氧分压（PaO2）与假手术组大鼠比较明显降低（P〈0．01）；辛伐他汀干预组大鼠6hPaO2与肺栓塞模型组大鼠比较明显升高（P〈0．05）。肺栓塞模型组大鼠6h肺小动脉eNOS蛋白表达较假手术组降低（P〈0．01），辛伐他汀干预组组大鼠6h肺小动脉eNOS蛋白表达较肺栓塞模型组明显升高（P〈0．05）。肺栓塞模型组大鼠各时间点血浆IL-6，TNF-α水平较假手术组有升高趋势（P〉0．05）。辛伐他汀干预组大鼠各时间点血浆IL．6、TNF—α水平较肺栓塞模型组大鼠略有降低（P〉0．05）。结论辛伐他汀干预可降低急性肺栓塞大鼠的mPAP和RvsP,减轻低氧血症，改善内皮细胞功能，但对血浆IL-6．TNF-α水平无影响。

Protective effect of simvastatin on acute pulmonary thromboembolism in rats

Objective To explore the possible mechanisms of protective effect of simvastatin on acute pulmonary embolism（APE） in rat. Methods Seventy-two male Sprague-Dawley rats were randomly divided into sham-operation group, pulmonary thromboembolism（PTE） group and statins intervention group（n=24 in each group）. Right ventricular systolic pressure（RVSP） and mean pulmonary arterial pressure （mPAP） were measured by right heart catheter at 2h, 6h, 24h after induction of PTE. Blood gas analysis was processed and immunohistochemical analysis was performed to study the changes of endothelial nitric oxide synthase leNOS in pulmonary vascellum at 6h following induction of PTE. ELISA kits were used to evaluate the level of interleukin-6（IL-6） and tumor necrosis factor-a（TNF-a） in plasma. Results MPAP and RVSP at each time point was increased in the PTE group compared with sham-operation group（P〈 0.01） and decreased in the statins intervention group compared with PTE group significantly（P〈 0.05）. Compared with PTE group, PaO2 in statins intervention group was increased significantly 6 h after induction of PTE（P 〈 0.05）. Compared with sham-operation group, eNOS protein expression in PTE group at 6h after induction was decreased significantly（P 〈 0.01）. Compared with PTE group, it increased significantly in statin group（P 〈 0.05）. Compared with sham-operation group, the plasma levels of IL-6 and TNF-tt at each time point in the PTE group were increased slightly（P 〉 0.05）, while decreased slightly with simavastatin pretreatment（P 〉 0.05）. Conclusion Pretreatment with simavastatin decreases RVSP and mPAP, and improves hypoxemia and endothelial function in the rats with PTE, while has no effect on IL-6 and TNF-a.