METHODS: Sprague-Dawley rats were randomly divided into the sham, pulmonary thromboembolism (PTE), and sildenafil groups. The sham and PTE groups received normal saline once daily via gavage for 14 consecutive days, whereas the sildenafil group received sildenafil (0.5 mg/kg/day) once daily via gavage for 14 consecutive days. Autologous emboli were prepared from blood samples collected from the left femoral artery of rats in each group on day 13, and autologous emboli were injected into the jugular vein cannula of rats in the PTE and sildenafil groups on day 14. Sham-treated rats received the same volume of saline. Right systolic ventricular pressure (RVSP) and mean pulmonary arterial pressure (MPAP) were used to assess pulmonary embolism, and western blotting and enzyme-linked immunosorbent assay were used to detect relevant markers.
RESULTS: The Rho kinase signaling pathway was significantly activated in rats with APE, and sildenafil significantly inhibited this activation.
CONCLUSIONS: Sildenafil protected against APE through inhibiting Rho kinase activity, thereby reducing pulmonary vasoconstriction and decreasing elevated pulmonary arterial pressure. These findings might provide new ideas for the clinical treatment of acute pulmonary thromboembolism.
方法:Sprague-Dawley大鼠随机分为假手术组,肺血栓栓塞症(PTE),和西地那非组。假手术组和PTE组每天一次灌胃生理盐水,连续14天,而西地那非组连续14天每天一次通过灌胃给予西地那非(0.5mg/kg/天).第13天取各组大鼠左股动脉血样制备自体栓子,第14天取PTE组和西地那非组大鼠颈静脉插管注射自体栓子。假治疗的大鼠接受相同体积的盐水。右心室收缩压(RVSP)和平均肺动脉压(MPAP)用于评估肺栓塞,免疫印迹和酶联免疫吸附试验检测相关标志物。
结果:APE大鼠Rho激酶信号通路显著激活,和西地那非显著抑制这种激活。
结论:西地那非通过抑制Rho激酶活性保护抗APE,从而减少肺血管收缩和降低肺动脉压升高。这些发现可能为急性肺血栓栓塞症的临床治疗提供新的思路。