Effects of renal denervation on monocrotaline induced pulmonary remodeling.
Effects of renal denervation on monocrotaline induced pulmonary remodeling.
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肾去神经支配对野百合碱诱导的肺重构的影响。
DOI：
10.18632/oncotarget.15154
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Shan Q
中科院分区：
文献类型：
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作者：
Liu Q;Song J;Lu D;Geng J;Jiang Z;Wang K;Zhang B;Shan Q
肺动脉高压(PAH)是一种进展迅速的疾病，可导致右心衰竭甚至死亡。肾素-血管紧张素-醛固酮系统(RAAS)和交感神经系统的过度活动导致了PAH的发生和发展。肾去神经(RDN)在PAH不同时期的作用尚未完全阐明。采用单次腹腔注射野百合碱(MCT，60 mg/kg)诱导雄性SD大鼠(n=40)肺重塑。MCT给药24小时后，一组大鼠接受RDN(RDN24小时，n=10)，MCT注射2周后，另10只大鼠接受RDN治疗(RDN2w，n=10)，其余20只大鼠分为MCT组和假手术组(MCT，n=20)。对照组8只，一次性腹腔注射生理盐水(60 mg/kg)，假手术组。35天后，采集组织和血样。组织学分析显示，与MCT组相比，RDN24小时组大鼠右室、肺组织和肺血管胶原体积分数明显减少，而RDN2w组大鼠右室、肺组织和肺血管胶原体积分数无明显变化。此外，早期的RDN处理显著降低了SNS活性和钝化了RAAS活性。重要的是，RDN治疗显著提高了存活率。综上所述，早期RDN治疗可以减轻心肺纤维化，因此可能是预防PAH发展的一种有前途的方法。
Pulmonary artery hypertension (PAH) is a rapidly progressive disorder, which leads to right heart failure and even death. Overactivity of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system accounts for the development and progression of PAH. The role of renal denervation (RDN) in different periods of PAH has not been fully elucidated. A single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg) was used to induce pulmonary remodeling in male Sprague Dawley rats (n = 40). After 24-hour of MCT administration, a subset of rats underwent RDN (RDN24h, n = 10); after 2-week of MCT injection, another ten rats received RDN treatment (RDN2w, n = 10) and the left 20 rats were divided to MCT group with sham RDN operation (MCT, n = 20). Eight rats in Control group received intraperitoneal injection of normal saline (60 mg/kg) once and sham RDN surgery. After 35 days, tissue and blood samples were collected. Histological analysis demonstrated that the collagen volume fraction of right ventricle, lung tissue and pulmonary vessel reduced significantly in RDN24h group but not in the RDN2w group, compared with MCT group. Moreover, the earlier RDN treatment significantly decreased SNS activity and blunted RAAS activation. Importantly, RDN treatment significantly improved the survival rate. In summary, earlier RDN treatment could attenuate cardio-pulmonary fibrosis and therefore might be a promising approach to prevent the development of PAH.