肾交感神经去除术对心肌肥厚和心肌纤维化的影响

 目的:观察肾交感神经去除术（renal sympathetic denervation, RDN）对心肌肥厚和心肌纤维化的影响，并探讨其可能机制。方法:选用12周龄的健康SD雄性大鼠60只，随机分为假手术组、假手术+RDN组、主动脉缩窄组、主动脉缩窄+RDN组，8周后用介入生理记录仪检测血流动力学和心功能指标，HE染色、苦味酸-天狼星红染色分别观察心肌肥厚和心肌纤维化情况，放射免疫分析法测量血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量。结果:与主动脉缩窄组相比，RDN可显著改善主动脉缩窄大鼠心脏舒张功能［左室舒张末期压力（LVEDP）：(8.03±1.66) mmHg vs(15.77±2.14) mmHg；等容舒张期左室压力下降最大速率（-dp/dt）：(7 793±587) mmHg/s vs(6 353±475) mmHg/s;P＜0.01］、防止其心肌肥厚和纤维化［左心室重量指数：3.340±0.121 vs4.244±0.102;心肌细胞面积：(332.9±28.9) μm2 vs(401.6±33.2) μm2；胶原容积分数：7.76%±0.85% vs12.48%±1.82%；P＜0.01］。然而，RDN不能降低主动脉缩窄大鼠的血压（P＞0.05）。RDN导致主动脉缩窄大鼠的血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量均明显减少（P＜0.01）。结论: RDN可以通过降低交感和肾素-血管紧张素系统活性直接抑制心肌肥厚和心肌纤维化，从而改善心脏功能。

Effect of renal sympathetic denervation on cardiac hypertrophy and fibrosis

AIM:To investigate the effect of renal sympathetic denervation (RDN) on cardiac hypertrophy and fibrosis and to explore the underlying mechanisms. METHODS:Male SD rats were randomly divided into 4 groups: sham, sham plus RDN, aortic constriction (AC) and AC plus RDN group (n=15 for each group). After the intervention for 8 weeks, the haemodynamic data and cardiac function were measured by a physiological recorder. The histological structure of the heart was evaluated by HE and picro-sirius red staining. The plasma concentration of norepinephrine (NE), renin activity, angiotensin II (Ang II) concentration and cardiac Ang II level were determined by radioimmunoassay. RESULTS:Compared with AC group, RDN improved cardiac diastolic function ［left ventricular end-diastolic pressure: (8.03±1.66) mmHg vs(15.77±2.14) mmHg; -dp/dt: (7 793±587) mmHg/s vs(6 353±475) mmHg/s; both P<0.01］, inhibited cardiac hypertrophy ［left ventricular index: 3.340±0.121 vs4.244±0.102； cardiomyocyte area: (332.9±28.9) μm2 vs(401.6±33.2) μm2; both P<0.01］ and attenuated cardiac fibrosis (collagen volume fraction: 7.76%±0.85% vs12.48%±1.82%; P<0.01) in aortic constricted rats. However, RDN didn’t cause significant reduction of blood pressure in aortic constricted rats (P>0.05). RDN prevented the AC-induced increase in the plasma NE concentration, renin activity, Ang II concentration and cardiac Ang II level. CONCLUSION: RDN may directly prevent cardiac hypertrophy and fibrosis and improve cardiac function via regulating the sympathomimetic activity and renin-angiotensin system.