内毒素和糖皮质激素对内源性硫化氢合成酶胱硫醚-γ-裂解酶表达的调节及其机制
发布时间：2019-01-28 20:12
【摘要】： 在哺乳动物的体内,含硫氨基酸在胱硫醚-γ-裂解酶(cystathionine-γ-lyase,CSE)的催化下可以产生内源性硫化氢(hydrogen sulfide, H2S)。内源性H2S具有广泛的生理调节功能,在炎症性疾病的发生发展过程中同样发挥着重要作用。在内毒素和感染性休克时,血浆H2S含量、体内多个组织内源性H2S的生成以及CSE的表达和活性均显著增加,而CSE表达上调的机制尚不明确,本研究第一部分首先在小鼠腹腔巨噬细胞系RAW264.7细胞证实了内毒素脂多糖(lipopolysaccharides,LPS)能够显著上调CSE mRNA和蛋白表达,继而研究了LPS诱导CSE表达的信号转导机制。结果发现, PKC、PI3K和NF-κB信号通路参与了LPS诱导CSE表达的过程。糖皮质激素(glucocorticoids, GCs)是临床常用的抗炎抗休克药物,已有大量资料表明GCs可以抑制体内另一种在内毒素和感染性休克中发挥重要作用的内源性气体分子一氧化氮生成以及一氧化氮合成酶的表达,然而GCs对内源性H2S的生成有何调节作用目前尚不清楚,因此本研究第二部分探讨了糖皮质激素(地塞米松,DEX)对RAW264.7细胞内CSE表达的调节作用。结果显示,DEX能够从显著抑制LPS诱导的CSE mRNA和蛋白表达,并显著抑制CSE启动子的转录激活。
[Abstract]:In mammals, sulfur-containing amino acids can produce endogenous hydrogen sulfide (hydrogen sulfide, H _ 2S) under the catalysis of cystathion-gamma lyase (cystathionine- 纬-lyase,CSE). Endogenous H _ 2S has a wide range of physiological regulatory functions, and also plays an important role in the occurrence and development of inflammatory diseases. During endotoxin and septic shock, the levels of H2S in plasma, endogenous H2S production in several tissues, and the expression and activity of CSE were significantly increased, but the mechanism of up-regulation of CSE expression was not clear. The first part of this study demonstrated that lipopolysaccharide (lipopolysaccharides,LPS) could significantly up-regulate the expression of CSE mRNA and protein in murine peritoneal macrophage cell line RAW264.7, and then studied the signal transduction mechanism of CSE expression induced by LPS. The results showed that PKC,PI3K and NF- 魏 B signaling pathway were involved in the process of CSE expression induced by LPS. Glucocorticoid (glucocorticoids, GCs) is a commonly used anti-inflammatory and anti-shock drug. It has been shown that GCs can inhibit the production of nitric oxide and the expression of nitric oxide synthase, another endogenous gas molecule that plays an important role in endotoxin and septic shock. However, it is not clear how GCs regulates the production of endogenous H2S, so the second part of this study is to explore the regulatory effect of dexamethasone, DEX) on the expression of CSE in RAW264.7 cells. The results showed that DEX could significantly inhibit the expression of CSE mRNA and protein induced by LPS and the transcriptional activation of CSE promoter.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363
本文编号：2417278
[Abstract]:In mammals, sulfur-containing amino acids can produce endogenous hydrogen sulfide (hydrogen sulfide, H _ 2S) under the catalysis of cystathion-gamma lyase (cystathionine- 纬-lyase,CSE). Endogenous H _ 2S has a wide range of physiological regulatory functions, and also plays an important role in the occurrence and development of inflammatory diseases. During endotoxin and septic shock, the levels of H2S in plasma, endogenous H2S production in several tissues, and the expression and activity of CSE were significantly increased, but the mechanism of up-regulation of CSE expression was not clear. The first part of this study demonstrated that lipopolysaccharide (lipopolysaccharides,LPS) could significantly up-regulate the expression of CSE mRNA and protein in murine peritoneal macrophage cell line RAW264.7, and then studied the signal transduction mechanism of CSE expression induced by LPS. The results showed that PKC,PI3K and NF- 魏 B signaling pathway were involved in the process of CSE expression induced by LPS. Glucocorticoid (glucocorticoids, GCs) is a commonly used anti-inflammatory and anti-shock drug. It has been shown that GCs can inhibit the production of nitric oxide and the expression of nitric oxide synthase, another endogenous gas molecule that plays an important role in endotoxin and septic shock. However, it is not clear how GCs regulates the production of endogenous H2S, so the second part of this study is to explore the regulatory effect of dexamethasone, DEX) on the expression of CSE in RAW264.7 cells. The results showed that DEX could significantly inhibit the expression of CSE mRNA and protein induced by LPS and the transcriptional activation of CSE promoter.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363
【引证文献】
相关期刊论文 前1条
1 陈超;高洪;严玉霖;陈利平;高利波;赵汝;陈玲;;内毒素血症中肝损伤与H_2S的关系及阳离子A的保护效应分析[J];畜牧兽医学报;2011年02期
，本文编号：2417278
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