Hydrogen Sulfide Alleviates Myocardial Collagen Remodeling in Association with Inhibition of TGF-β/Smad Signaling Pathway in Spontaneously Hypertensive Rats
Hydrogen Sulfide Alleviates Myocardial Collagen Remodeling in Association with Inhibition of TGF-β/Smad Signaling Pathway in Spontaneously Hypertensive Rats
复制标题
硫化氢减轻自发性高血压大鼠的心肌胶原重塑并抑制 TGF-β/Smad 信号通路
DOI：
10.2119/molmed.2013.00096
复制
发表时间：
2014-07-01
影响因子：
5.7
通讯作者：
Du, Junbao
中科院分区：
文献类型：
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作者：
Sun, Lili;Jin, Hongfang;Du, Junbao
本研究旨在探讨硫化氢（H2S）在自发性高血压大鼠（SHRs）心肌胶原重构中的作用及其可能机制。我们用NaHS （90 μ mol/kg(-1)）治疗9周龄雄性SHRs和年龄和性别匹配的Wistar-Kyoto大鼠（WKYs）。天（-1）)连续9周。18周时，测定大鼠血浆H2S、尾动脉压、心脏形态、心肌超微结构和胶原体积分数（CVF）、心肌I、III型胶原蛋白和I、III型前胶原mRNA表达、转化生长因子- β 1 （tgf - β 1）、tgf - β I型受体（T β R-I）、II型受体（T β R-II）、p-Smad2和3、基质金属蛋白酶(MMP)-13和MMP -1蛋白组织抑制剂(TIMP)-1。利用tgf - β 1刺激培养的心脏成纤维细胞（CFs）进一步研究其机制。结果显示，与WKYs相比，SHRs降低了血浆H2S，尾动脉压升高，心肌胶原蛋白、tgf - β 1、T β R-II、p-Smad2和p-Smad3表达升高。NaHS可显著降低尾动脉压，抑制心肌胶原、tgf - β 1、T β R-II、p-Smad2、p-Smad3蛋白表达，而H2S对MMP-13、TIMP-1表达无影响。海氮嗪降低血压，但对心肌胶原蛋白、MMP-13、TIMP-1表达及tgf - β 1/Smad信号通路无影响。H2S可以阻止tgf - β 1/Smad信号通路的激活和CFs中胶原合成的异常。由此可见，H2S对SHR大鼠心肌胶原重构具有一定的抑制作用。其机制可能与tgf - β 1/Smad信号通路抑制胶原合成有关。
The study was designed to explore the role and possible mechanisms of hydrogen sulfide (H2S) in the regulation of myocardial collagen remodeling in spontaneously hypertensive rats (SHRs). We treated nine-week-old male SHRs and age-and sex-matched Wistar-Kyoto rats (WKYs) with NaHS (90 mu mol/kg(-1).day(-1)) for 9 wks. At 18 wks, plasma H2S, tail arterial pressure, morphology of the heart, myocardial ultrastructure and collagen volume fraction (CVF), myocardial expressions of collagen I and III protein and procollagen I and III mRNA, transforming growth factor-beta 1 (TGF-beta 1), TGF-beta type I receptor (T beta R-I), type II receptor (T beta R-II), p-Smad2 and 3, matrix metalloproteinase (MMP)-13 and tissue inhibitors of MMP (TIMP)-1 proteins were determined. TGF-beta 1-stimulated cultured cardiac fibroblasts (CFs) were used to further study the mechanisms. The results showed that compared with WKYs, SHRs showed a reduced plasma H2S, elevated tail artery pressure and increased myocardial collagen, TGF-beta 1, T beta R-II, p-Smad2 and p-Smad3 expressions. However, NaHS markedly decreased tail artery pressure and inhibited myocardial collagen, TGF-beta 1, T beta R-II, p-Smad2 and p-Smad3 protein expressions, but H2S had no effect on the expressions of MMP-13 and TIMP-1. Hydralazine reduced blood pressure but had no effect on myocardial collagen, MMP-13 and TIMP-1 expressions and TGF-beta 1/Smad signaling pathway. H2S prevented activation of the TGF-beta 1/Smad signaling pathway and abnormal collagen synthesis in CFs. In conclusion, the results suggested that H2S could prevent myocardial collagen remodeling in SHR. The mechanism might be associated with inhibition of collagen synthesis via TGF-beta 1/Smad signaling pathway.