肾去交感神经对肺动脉高压模型犬肺血管重构的影响

Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension

目的探讨肾去交感神经（RSD）对肺动脉高压（PAH）模型犬肺血管重构的影响。方法24只比格犬按随机数字表法随机均分为对照组、PAH组、PAH＋RSD组各8只。检测各组犬实验前血清神经激素水平、心脏超声和血流动力学参数后，对照组右心房注入二甲基甲酰胺（0．1ml／kg），PAH组右心房注入脱氢野百合碱（2ml／kg），PAH＋RSD组先行肾去交感神经术，后右心房注入脱氢野百合碱（2ml／kg）。喂养8周，检测各组犬实验后的血清神经激素水平、心脏超声和血流动力学参数后，开胸取肺组织检测肺血管形态学。结果实验后PAH组、PAH＋RSD组右心室收缩压（RVSP）和肺动脉收缩压（PASP）均显著高于对照组[（42．8±8．7）、（30．8±6．8）比（23．2±5．7）mmHg（1mmHg=0．133kPa）和（45．1±11．2）、（32．6±7．9）比（24．7±7．1）mmHg]，且PAH组RVSP和PASP显著高于PAH＋RSD组[均P〈0．01]。实验后PAH组血清血管紧张素Ⅱ（AngⅡ）和内皮素1水平均显著高于实验前[（228±41）比（113±34）pg／ml和（135±15）比（77±7）pg／ml，均P〈0．01]，且肺组织中AngU和内皮素1水平[（65±10）和（96±10）pg／ml]均显著高于对照组[（38±7）和（54±6）pg／m1]和PAH＋RSD组[（46±8）和（67±9）pg／m1]（均P〈0．01）。与对照组相比，PAH组肺泡2型细胞破坏严重，组织纤维化明显，而PAH＋RSD组肺泡2型细胞破坏及组织纤维化较PAH组轻。结论RSD可降低PAH模型犬肺动脉高压并抑制肺血管重构，此作用可能与其降低神经激素水平有关。

Objective To explore the effects of renal sympathetic denervation （RSD） on pulmonary vascular remodeling in a model of pulmonary arterial hypertension （ PAH ）. Methods According to the random number table, 24 beagles were randomized into control, PAH and PAH ＋ RSD groups （n = 8 each）. The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0. 1 ml/kg dimethylformamide （control group） or 2 mg/kg dehydromonocrotaline （PAH and PAH ＋ RSD groups） were injected. The PAH ＋ RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. Results The values of right ventricular systolic pressure （RVSP） and pulmonary arterial systolic pressure （PASP） in PAH and PAH ＋ RSD groups were both significantly higher than those in control group （ （ 42. 8 ± 8. 7 ） , （30.8±6.8） vs （23.2±5.7） mmHg （1 mmHg=0.133 kPa） and （45.1 ±11.2）, （32.6±7.9） vs （24. 7 ±7. 1 ） mmHg）. Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH ＋ RSD group （ all P 〈 0. 01 ）. The levels of serum angiotensin Ⅱ （Ang Ⅱ ） and endothelin-1 significantly increased after 8 weeks in PAH dogs （（ 228 ± 41 ） vs （113 ± 34 ） pg/ml and （135 ± 15 ） vs （77 ±7） pg/ml, all P 〈 0.01 ）. And Ang Ⅱ and endothelin-1 were higher in lung tissues of PAH group （（65±10） and （96±10） pg/ml） than in those of control group （（38 ±7） and （54±6） pg/ml） andPAH ＋ RSD group （ （46 ±8） and （67±9） pg/ml） （all P 〈0. 01 ）. Pulmonary tissues had marked collagen hyperplasia and lamellar corpuscles of type 2 alveolar cells were damaged more severely in PAH dogs than in PAH ＋ RSD dogs. Conclusions RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.