硫化氢供体对动脉粥样硬化大鼠肾上腺髓质素及心钠素的影响

Effects of hydrogen sulfide donor on production of adrenomedullin and atrial natriuretic peptide in rats with atherosclerosis

摘要:

目的 内源性硫化氢(H₂S) 作为心血管调节的新型气体信号分子,在动脉粥样硬化(AS)发生发展中发挥重要保护作用。本研究拟探讨H₂S 供体对AS 大鼠肾上腺髓质素(ADM)和心钠素(ANP)的影响。方法 雄性SD 大鼠随机分为对照组、AS 组和AS+NaHS 组。AS 组和AS+NaHS 组大鼠给予连续3 d 腹腔注射维生素D₃ 及高脂饲料连续喂养8 周。AS+NaHS 组大鼠腹腔注射H₂S 供体NaHS。油红O 染色法观察大鼠主动脉根部及冠状动脉斑块面积变化;敏感硫电极法测量血浆H₂S 含量;放射免疫法检测血浆ADM 及ANP 含量。结果 与对照组相比,AS 大鼠主动脉根部及冠状动脉可见明显AS 斑块形成,血浆H₂S 含量明显降低,ADM 含量升高,ANP 含量明显降低(P<0.01)。给予NaHS 干预8 周后,AS 大鼠的上述改变被逆转,表现为AS+NaHS组大鼠主动脉根部和冠状动脉AS 斑块面积明显缩小,血浆H₂S 含量明显升高,ADM 含量明显降低,ANP 含量显著升高(P<0.01)。结论 H₂S 对AS 大鼠血管活性多肽ADM、ANP 具有重要的调节作用。

Abstract:

Objective Endogenous hydrogen sulfide (H₂S), a novel gasotransmitter in cardiovascular regulation, plays an important protective role in the development and progression of atherosclerosis (AS). This study was designed to explore the effects of H₂S donor on the production of adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in AS rats. Methods Male Sprague-Dawley rats were randomly divided into control group (n=10), AS group (n=10), and AS+NaHS group (n=10). Rats in the AS and AS+NaHS groups were given 3-day intraperitoneal injections of vitamin D₃ and 8-week high-fat diet to induce AS, and the rats in the AS+NaHS group were intraperitoneally injected with H₂S donor NaHS. Oil red O staining was applied to detect changes in the areas of the atherosclerotic plaques in the aortic root and the coronary artery;sulfide-sensitive electrode method was used to measure the plasma concentration of H₂S. ADM and ANP levels in plasma were determined by radioimmunoassay. Results Compared with the control group, marked atherosclerotic plaques were observed in the aortic root and the coronary artery in AS rats. Moreover, plasma H₂S level decreased significantly, ADM level increased, and ANP level decreased significantly in AS rats (P<0.01). However, after the treatment with H₂S donor NaHS for 8 weeks, the above changes in AS rats were reversed, demonstrated by significantly reduced areas of the atherosclerotic plaques in both the aortic root and the coronary artery, significantly increased plasma H₂S level, significantly decreased plasma ADM level, and significantly increased plasma ANP level (P<0.01). Conclusions H₂S plays an important regulatory effect on vasoactive peptides ADM and ANP in AS rats.