硫氢化钠对慢性心力衰竭大鼠心脏功能和肾素-血管紧张素-醛固酮系统活性的影响

目的:探讨硫氢化钠(Na HS)对慢性心力衰竭(chronic heart failure,CHF)大鼠心脏功能和肾素(renin)-血管紧张素(Ang)-醛固酮(ALD)系统(RAAS)活性的影响。方法:本研究通过腹主动脉缩窄术构建CHF大鼠模型,将SD大鼠随机分为假手术组、模型组、Na HS低剂量组和Na HS高剂量组,每组6只。采用超声心动图检测每组大鼠治疗前及治疗结束后的左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)和左心室射血分数(LVEF)。治疗结束后,采用ELISA试剂盒检测各组大鼠血浆中renin、AngⅡ和ALD的浓度。采用q PCR和Western blot实验分别检测各组大鼠心肌组织中血管紧张素转换酶(ACE)和血管紧张素Ⅱ1型受体(AT1R)的mRNA和蛋白表达。结果:经Na HS治疗后,与模型组和治疗前相比,Na HS低剂量组和Na HS高剂量组的LVEDD和LVESD均明显降低,而LVEF明显升高(P0.05);与Na HS低剂量组相比,Na HS高剂量组的LVEDD和LVESD降低,而LVEF升高(P0.05)。与假手术组相比,模型组大鼠血浆中renin、AngⅡ和ALD浓度显著升高(P0.05),心肌组织中ACE和AT1R的mRNA和蛋白表达显著上调(P0.05);与模型组相比,Na HS低剂量组和Na HS高剂量组大鼠血浆renin、AngⅡ和ALD浓度显著降低(P0.05),心肌组织中ACE和AT1R的mRNA和蛋白表达显著下调(P0.05);Na HS高剂量组大鼠血浆renin、AngⅡ和ALD浓度及心肌组织中ACE和AT1R的mRNA和蛋白表达显著低于Na HS低剂量组(P0.05)。结论:Na HS可通过抑制RAAS的活性改善CHF大鼠的心功能,且高剂量组的改善效果优于低剂量组。

Effects of sodium hydrosulfide on cardiac function and activity of renin-angiotensin-aldosterone system in rats with chronic heart failure

AIM: To investigate the effect of sodium hydrosulfide (NaHS) on cardiac function and activity of renin-angiotensin (Ang)-aldosterone (ALD) system (RAAS) in the rats with chronic heart failure (CHF).METHODS: The CHF rat model was established by abdominal aortic coarctation. SD rats were randomly divided into sham operation group, model group, low dose of NaHS group and high dose of NaHS group (n=6). The left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were measured before and after treatment by echocardiography in each group. The levels of renin, AngⅡ and ALD in the plasma were measured by ELISA. The expression of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) at mRNA and protein levels in the myocardium tissues was determined by qPCR and Western blot, respectively.RESULTS: After treatment with NaHS, compared with model group and before treatment, LVEDD and LVESD in low dose of NaHS group and high dose of NaHS group were decreased significantly, while LVEF was increased significantly (P<0.05). Compared with low dose of NaHS group, LVEDD and LVESD were decreased, while LVEF was increased in high dose of NaHS group (P<0.05). Compared with sham operation group, the levels of renin, AngⅡ and ALD in the plasma of model group were significantly increased (P<0.05), and the expression of ACE and AT1R at mRNA and protein levels in the myocardium tissues of model group were significantly increased (P<0.05). Compared with model group, the plasma levels of renin, AngⅡ and ALD in low dose of NaHS group and high dose of NaHS group were significantly decreased (P<0.05), and the myocardial expression of ACE and AT1R at mRNA and protein levels was significantly down-regulated (P<0.05). The plasma levels of renin, AngⅡ and ALD, and the myocardial expression of ACE and AT1R at mRNA and protein levels in high dose of NaHS group were significantly lower than those in low dose of NaHS group (P<0.05).CONCLUSION: NaHS inhibits the activation of RAAS, thus improving the cardiac function of CHF rats, and the effect of high-dose NaHS is better than that of low-dose NaHS.