Effect of fasudil combined with sildenafil in the treatment of pulmonary hypertension in rats

Abstract

Abstract:

AIM: To investigate the curative effect of fasudil combined with sildenafil in the treatment of pulmonary hypertension in rats. METHODS: 100 rats were randomly divided into A, B, C, D and E group.Group A was control group, group B was set for the model of pulmonary hypertension, group C was given fasudil treatment on the basis of modeling. Group D received sildenafil treatment on the basis of modeling, group E was given fasudil combined with sildenafil treatment on the basis of modeling. The blood pressure, right ventricular function, right ventricular hypertrophy and vascular reconstruction were compared between the 5 groups. RESULTS:The RVSP of C group, D group and E group were significantly lower than that of B group；the RVSP of E group was significantly lower than that of rats in the C group (P<0.05); RVEDD and RVESD of group E were significantly lower than those in the C group, and right ventricular fractional shortening of D group and E group were significantly higher than that in the B group (P<0.05); RV/LV+S and RV/BW of the rats in group E were significantly lower than that of C group and group D (P<0.05); pulmonary artery intimal thickening in rats of group E was significantly lower than that of B group, C group and D group (P<0.05).Rho kinase activity in pulmonary artery of E group was significantly lower than that of B group, C group and D group (P<0.05). CONCLUSION: Fasudil combined with sildenafil treatment can significantly improve the hemodynamics of rats with pulmonary hypertension and right ventricular function as well as relieve right ventricular hypertrophy.It is beneficial to microvascular reconstruction, and there is a cooperative relationship between the two drugs in the regulation of Rho kinase activity and the treatment of pulmonary artery.

Key words: fasudil, sildenafil, pulmonary hypertension

CLC Number:

R965.2

XU Jing, JIN Xiaojie. Effect of fasudil combined with sildenafil in the treatment of pulmonary hypertension in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(3): 281-286.

References

［1］朱兴旺, 朱小冰. 吸入一氧化氮治疗新生儿持续性肺动脉高压研究进展［J］. 中国新生儿科杂志, 2015, 30(3): 236-240.
［2］Lam CS, Roger VL, Rodeheffer RJ, et al. Pulmonary hypertension in heart failure with preserved ejection fraction : a community-based study ［J］. J Am Col Cardiol, 2014, 7(2): 1047-1052.
［3］黄颖, 蓝登科, 张熹煜, 等. 从痰瘀论治慢性阻塞性肺疾病急性加重期并呼吸衰竭［J］. 长春中医药大学学报, 2016, 32(4): 742-744.
［4］Satoh K, Fukumoto Y, Sugimura K, et al. Plasma cyclophilin A is a novel biomarker for coronary artery disease［J］. Circul J Offic J Jpn Circul Soc, 2012, 77(2): 447-455.
［5］周永清. 黄芪注射液对慢性阻塞性肺疾病加重期患者细胞因子及肺功能的影响［J］. 长春中医药大学学报, 2016, 32(2):337-338.
［6］高汉华, 刘映峰, 钟华英, 等. 川芎嗪联合西地那非对原发性肺动脉高压导致右心室重塑的影响［J］. 中国老年学, 2014,34(9):2383-2385.
［7］Fukumoto Y, Shimokawa H. Recent progress in the management of pulmonary hypertension［J］. Circul J Offic J Jpn Circul Soc, 2011, 75(8):1801-1810.
［8］Voelkel NF, Gomez-Arroyo J, Abbate A, et al. Pathobiology of pulmonary arterial hypertension and right ventricular failure ［J］. Euro Res J, 2012, 40(6): 1555-1565.
［9］Aguero J, Ishikawa K, Hadri L, et al. Intratracheal gene delivery of SERCA2a ameliorates chronic post-capillary pulmonary hypertension: a large animal model ［J］. J Am Col Cardiol, 2016, 67(17): 2032.
［10］Lewis GD, Ngo D, Hemnes AR, et al. Metabolic profiling of right ventricular-pulmonary vascular function reveals circulating biomarkers of pulmonary hypertension.［J］. J Am Col Cardiol, 2016, 67(2): 174-189.
［11］Shimokawa H. Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension; a pilot efficacy trial ［J］. Circul J Offic J Jpn Circul Soc, 2013, 77(10): 2619-2625.
［12］Liu AJ, Ling F, Wang D, et al. Fasudil inhibits platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation by up-regulation of p27kip1 via the ERK signal pathway［J］. Chin Med J, 2011, 125(19): 3098-3104.
［13］Lewis GD, Ngo D, Hemnes AR, et al. Metabolic profiling of right ventricular-pulmonary vascular function reveals circulating biomarkers of pulmonary hypertension ［J］. J Am Col Cardiol, 2016, 67(2): 174-189.
［14］Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology ［J］. Euro J Heart Fail, 2016, 18(9): 1119-1128.
［15］Bertero T, Lu Y, Annis S, et al. Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension ［J］. J Clin Invest, 2014, 124(8): 3514-3528.

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