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101.
目的:比较波生坦和氨氯地平对脱氧皮质酮(DOCA)-盐型高血压大鼠(DHR)肾脏纤维化和微血管的影响,探讨内皮素-1(ET-1)在DHR肾脏损害中的作用及可能机制。方法:30只10周龄清洁级雄性SD大鼠,切除左侧肾脏,1周后存活24只,随机分成对照组、波生坦组、氨氯地平组和安慰剂组。对照组给予饮自来水,另3组予DOCA[50mg/(kg·周)]皮下注射,饮盐水,同时分别予波生坦、氨氯地平和安慰剂;5周时测定24h尿蛋白排泄量(24h-UPER)、血压、尿素氮(BUN)和血肌酐(Scr);处死后评估病理切片肾小球硬化和肾小管间质损害程度;观察转化生长因子β1(TGF-β1)和Smad7的表达,分析肾组织毛细血管指数和增生内皮细胞数。结果:与对照组相比,安慰剂组血压、24h-UPER增加,肾脏有较明显的组织学改变,肾内TGF-β1和Smad7的蛋白表达明显上调,波生坦能较显著地抑制上述异常(P0.05)。各组肾功能指标在正常范围内。安慰剂组中肾小球毛细血管指数(GCI)和肾小管周毛细血管指数(PCI)和增生内皮细胞数较对照组明显减少,波生坦、氨氯地平均能显著增加毛细血管和新生毛细血管数(P<0.01),但氨氯地平组增加程度不如波生坦组,差异有统计学意义(P<0.05)。TGF-β1与GCI、PCI和增生内皮细胞数具有显著的负相关性。结论:ET-1在DHR肾脏损害中发挥重要作用,其机制可能为通过上调TGF-β1和Smad7蛋白表达及直接抑制新生血管形成,间接加速毛细血管毁损而加重肾缺血和肾损害。 相似文献
102.
波生坦对儿童先天性心脏病相关肺动脉高压的治疗作用 总被引:1,自引:0,他引:1
目的 观察波生坦在儿童先天性心脏病(CHD)相关肺动脉高压(PAH)患儿中应用的疗效及安全性,评价波生坦治疗儿童CHD-PAH的临床效果.方法 入选2008年1月至2011年5月首都医科大学附属北京安贞医院小儿心脏科入院≤18岁CHD-PAH患儿23例,给予波生坦口服治疗,进行开放性、观察性研究.随访评估服药前后6 min步行试验距离(6MWTD)、经皮血氧饱和度(SpO2)、纽约心脏病学会心功能分级(NYHA-FC)、心导管检查血流动力学参数(平均肺动脉压、肺小动脉阻力指数、肺体循环流量比、肺体循环阻力比)及肝功能变化.结果入选儿童患儿23例,平均年龄为(9.1±3.6)岁(2.1~14.7岁).口服波生坦治疗平均时间(13.3±7.5)个月(6 ~31个月).治疗后,11例患儿(年龄7岁以上)的6MWTD从(458±16)m增加至(496±49)m(P =0.035).23例患儿的SpO2 (89 ±6)%提高到(91±5)%(P=0.009).此外,所有患儿的NYHA心功能分级有不同程度改善或保持稳定.12例服药后再次接受心导管检查的患儿,肺、体循环比( Qp/Qs)由服药前平均(0.97 ±0.38)增至(1.16±0.39)(P =0.076),平均肺动脉压(mPAP)由(76±6)mm Hg(1 mm Hg=0.133 kPa)增至(78±12)mm Hg(P =0.649),肺小动脉阻力指数( PVRi)由平均(20.78±8.84) Woods units/m2降至( 18.13±7.71) Woods units/m2(P=0.165),肺、体循环阻力比(Rp/Rs)由(1.03±0.38)降至(0.83±0.29)(P=0.06),以上指标均有不同程度改善,但差异无统计学意义.所有患儿均对波生坦良好耐受,仅1例10岁男性患儿有一过性鲜血便.结论 服用波生坦可明显改善CHD-PAH患儿的6MWT、SpO2、NYHA-FC,降低PVR及Rp/Rs.波生坦在不符合手术适应证的儿童CHD-PAH患儿中的应用是安全、有效的. 相似文献
103.
目的观察波生坦在围手术期治疗先天性心脏病婴儿合并中、重度肺动脉高压中的效果。方法将60例1月~1岁先天性心脏病合并肺动脉高压的婴儿,随机分为两组。A组30例接受常规治疗,B组30例在常规治疗基础上加用波生坦口服治疗,术前6.25 mg,2/d,应用7天;术后12.5 mg,2/d,应用1~4周。记录两组用药前、用药后1周和术后治疗1周时的肺动脉收缩压,比较两组术后机械辅助通气时间,评价波生坦的疗效。结果 B组肺动脉收缩压较A组持续下降(P=0.002);术后机械辅助通气时间较A组显著缩短。结论波生坦在婴儿先天性心脏病合并中、重度肺动脉高压围术期中的应用安全有效。 相似文献
104.
Utku Arman Orun MD Osman Yilmaz MD Meki Bilici MD Selmin Karademir MD Cigdem Uner MD Filiz Senocak MD Vehbi Dogan MD 《Congenital heart disease》2012,7(3):E6-E9
Unilateral pulmonary artery agenesis is a rare congenital anomaly caused by a backward displacement of the conical artery of the truncus arteriosus. It is commonly associated with additional cardiovascular abnormalities. A 7‐year‐old girl was admitted to our clinic with the complaint of shortness of breath upon exertion. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery with atrial septal defect and pulmonary hypertension was demonstrated by echocardiography, computed tomography, and cardiac catheterization. Bosentan is effectively used to treat pulmonary arterial hypertension. 相似文献
105.
《Revista portuguesa de cardiologia》2014,33(4):213-222
Introduction and ObjectivesEndothelin-1 antagonists are increasingly used in the treatment of pulmonary hypertension despite the lack of knowledge of their myocardial and systemic effects. We assessed the right ventricular myocardial and systemic effects of endothelin-1 antagonists in monocrotaline-induced pulmonary hypertension.MethodsMale Wistar rats (180–200 g, n=57) randomly received 60 mg/kg monocrotaline or vehicle subcutaneously. Two days later, bosentan was randomly started (300 mg/kg/day) by oral route in a subgroup of monocrotaline-injected rats, while the other monocrotaline-injected and control rats received vehicle. At 25–30 days, invasive hemodynamic assessment was performed under anesthesia, arterial blood samples were collected for gas analysis and plasma was extracted for quantification of endothelin-1, cytokines, nitrates and 6-keto-prostaglandin F1α. Right ventricular myocardium was collected for assessment of cyclooxygenase and nitric oxide synthase activity and gene expression.ResultsThe monocrotaline group developed pulmonary hypertension, low cardiac output, right ventricular hypertrophy and dilation, changes in gene expression and inflammatory activation that were attenuated in the group treated with bosentan. From a functional point of view, this group had improved right ventricular function and preserved ventriculo-vascular coupling, without deterioration in arterial gas parameters or systemic hypotension. In molecular terms, they showed reduced endothelin-1 and cytokine levels, decreased right ventricular inducible nitric oxide synthase and cyclooxygenase-2 activity and increased nitrate plasma levels compared with the non-treated group.ConclusionsIn this study we demonstrate that besides attenuating pulmonary hypertension, bosentan has beneficial hemodynamic, myocardial and anti-inflammatory effects. 相似文献
106.
107.
First experience with an oral combination therapy using bosentan and sildenafil for pulmonary arterial hypertension 总被引:3,自引:0,他引:3
108.
109.
Andreas Ambach Won Seo Bernd Bonnekoh Harald Gollnick 《Journal der Deutschen Dermatologischen Gesellschaft》2009,7(10):888-891
Digital ulcers in progressive systemic sclerosis (PSS) are often refractory to therapy. A frequently chronic aggressive course can lead to the loss of acral limbs involved. A 73‐year‐old woman developed a dramatic worsening of her ulcerations despite maximum conventional therapy. Switching therapy to bosentan and sildenafil, both in low‐dose regimens, resulted for the first time in ten years in a complete healing of the ulcers. If substantiated in a series of patients, the additive and perhaps synergistic clinical benefits of combining bosentan and sildenafil may be a valuable option for the treatment of acral ulcers in PSS. 相似文献
110.
We present a case of the successful use of bosentan for increased pulmonary vascular resistance (PVR) in a 10-year-old male
who underwent late single ventricle surgical palliation for double-inlet left ventricle with pulmonary artery banding and
a bidirectional Glenn shunt. The patient was treated with bosentan for 16 weeks, with decreases in mean pulmonary artery pressure
from 23 to 16 mmHg on the right and from 31 to 21 mmHg on the left, and a decrease of the transpulmonary gradient by 7–8 mmHg.
Cardiopulmonary exercise testing demonstrated an increase in peak oxygen consumption (VO2) by 8% and peak work rate by 10%. Bosentan is a relatively new oral therapy option for increased PVR in patients with single
ventricle physiology and bidirectional Glenn shunts. 相似文献