Hydrogen Sulfide Attenuates Abdominal Aortic Coarctation Induced Cardiac Hypertrophy and Fibrosis in Rats
|Course||Department of Cardiology|
|Keywords||Hydrogen sulfide Cardiac hypertrophy Angiotensin - II|
BACKGROUND AND PURPOSE: The following nitric oxide (nitrogen monoxidum NO) and carbon monoxide (carbon oxide, CO) recently discovered third No. endogenous gaseous signaling molecule hydrogen sulfide (hydrogen sulfide, H2S), a variety of pathological vivo physiological processes play an important role in the regulation. Especially in the cardiovascular system, H2S has a specific role in the physiological regulation. Cardiac hypertrophy is the common diseases of the cardiovascular system, and is also an independent risk factor for deterioration of cardiac function and sudden cardiac death, and thus cardiac hypertrophy subsided, can effectively reduce the morbidity and mortality of cardiovascular diseases. The study confirmed that the renin - angiotensin system (renin-angiotensin system, RAS) development plays an important role in myocardial hypertrophy. To this end, the experiment by partial ligation of the abdominal aorta, the establishment of cardiac hypertrophy model thus observed in H2S intervention, cardiac hypertrophy, fibrosis, cardiac, circulatory angiotensin - Ⅱ (Ang-Ⅱ) expression change and connexin 43 (Connexin 43, Cx43) content changes, so as to explore the the H2S ability to improve the pressure overload-induced cardiac hypertrophy, fibrosis, as well as the related mechanisms. Materials and Methods: The experimental animals for the Sprague-Dawley 8-week-old male rats (170-190 g) were randomly divided into normal control group (n = 10), sham group (n = 10) and model group (n = 80 ), model group rats the reported abdominal aortic ligation, one week later, survival, rats were randomly divided into simple ligation group (n = 14), ligation enalapril group (n = 14) (enalapril gastric feeding administration, 5mg/kg/d), ligation of the hydrogen sulfide group (n = 14) the (hydrogen sulfide intraperitoneal administration by injection, 14umol/kg/d). Sham group only separation of the abdominal aorta, ligation, and the other dealing with the model group. One week after ligation in rats, administered early in the morning, were killed after feeding four weeks. Respectively the abdominal aorta blood and rat myocardial do the following test: 1. Determine cardiac hypertrophy through the detection of left ventricular mass index (LVW / BW); 2 by hematoxylin - eosin staining, detection of myocardial cells shortest diameter cross-sectional area to determine the myocardial cell hypertrophy situation; 3. Sirius red staining, the degree of myocardial collagen deposition and collagen volume fraction from the observed morphology; determine myocardial collagen by alkaline hydrolysis method for detecting myocardial hydroxyproline content, content. By enzyme-linked immunosorbent assay, detected in plasma and myocardial tissue angiotensin - Ⅱ content. By immunohistochemical methods, detection of cardiac gap junction protein 43 expression. 6 methylene blue spectrophotometric determination of the endogenous H2S content. Results: Compared with the sham group, compared with simple ligation rats increased left ventricular mass and left ventricular mass index of 35.26%, respectively (P lt; 0.05), 25% (P lt; 0.05); ligation group each, in accordance with enalapril (5mg/kg/d) group of left ventricular mass and left ventricular mass index decreased by 23.4% (P lt; 0.05), 6.38% (P lt; 0.05). Sodium hydrosulfide (14umol/kg/d, hydrogen sulfide donor) after intraperitoneal injection of 4 weeks, each left ventricular mass and left ventricular mass index fell by 14.9% (P lt; 0.05), 4.49% (P lt; 0.05) . 2, compared with sham group, model group rat cardiac myocyte cross-sectional area increases 94.59% (P lt; 0.01). Than a simple ligation group, according to the the enalapril group cardiac myocyte cross-sectional area is reduced by 25.48% (P lt; 0.05). Meanwhile, the intraperitoneal injection of sodium hydrosulfide, for 4 weeks, the myocardial cell area is reduced by 15.97% (P LT; 0.05). 3, compared with the sham group rats, the collagen volume fraction increased by 60% (P lt; 0.05), myocardial hydroxyproline content increased by 58% (P lt; 0.05). Given enalapril and hydrogen sulfide fed for four weeks, compared with ligation group, the left ventricular endocardial and epicardial myocardial collagen density was significantly lower the CVF were reduced by 24% (P lt; 0.05), 17.9 % (P lt; 0.05), myocardial hydroxyproline content were reduced by 31.4% (P lt; 0.05), 39.1% (P lt; 0.05). Simple ligation group myocardial expression of Ang-Ⅱ compared with sham group increased by 29.3% (P lt; 0.05); enalapril the Plymouth group than simple ligation group content decreased by 12.28% (P lt; 0.05), hydrogen sulfide group than in the ligation group decreased by 17.47% (P lt; 0.05), while plasma Ang-Ⅱ expression in groups no significant difference (P gt; 0.05). 5, the the simple ligation rats connexin 43 expression was significantly decreased; while significantly improved by enalapril group and hydrogen sulfide group compared with ligation group. 6, abdominal aortic ligation after five weeks, compared with the sham group the the endogenous H2S content decreased by 7.65% (P lt; 0.05). Than simple ligation group increased by enalapril group of endogenous H2S content 4.27% (P lt; 0.05); simultaneously given NaHS fed for four weeks, The elevated endogenous H2S content of 3.65% (P lt; 0.05 ). Conclusion: 1, abdominal aortic ligation of the left ventricular hypertrophy significantly, the degree of fibrosis was significantly elevated significantly weakened enalapril of Plymouth (5mg/kg/d) and hydrogen sulfide (14umol/kg/d), left ventricular hypertrophy, lower of myocardial fibrosis. 2, abdominal aortic ligation of the gap junction protein 43 expression in decline, the Enalapril and hydrogen sulfide can improve the expression of Cx43. 3, the activation of the abdominal aorta ligation rat cardiac renin - angiotensin system (RAS), increased myocardial expression of Ang-Ⅱ; enalapril and hydrogen sulfide significantly down-regulated the expression of Ang-Ⅱ. Suggesting that hydrogen sulfide improve myocardial hypertrophy, fibrosis may the myocardial RAS, has nothing to do with the circulating RAS.