內(nèi)毒素和糖皮質(zhì)激素對內(nèi)源性硫化氫合成酶胱硫醚-γ-裂解酶表達的調(diào)節(jié)及其機制
發(fā)布時間：2019-01-28 20:12
【摘要】： 在哺乳動物的體內(nèi),含硫氨基酸在胱硫醚-γ-裂解酶(cystathionine-γ-lyase,CSE)的催化下可以產(chǎn)生內(nèi)源性硫化氫(hydrogen sulfide, H2S)。內(nèi)源性H2S具有廣泛的生理調(diào)節(jié)功能,在炎癥性疾病的發(fā)生發(fā)展過程中同樣發(fā)揮著重要作用。在內(nèi)毒素和感染性休克時,血漿H2S含量、體內(nèi)多個組織內(nèi)源性H2S的生成以及CSE的表達和活性均顯著增加,而CSE表達上調(diào)的機制尚不明確,本研究第一部分首先在小鼠腹腔巨噬細胞系RAW264.7細胞證實了內(nèi)毒素脂多糖(lipopolysaccharides,LPS)能夠顯著上調(diào)CSE mRNA和蛋白表達,繼而研究了LPS誘導CSE表達的信號轉(zhuǎn)導機制。結(jié)果發(fā)現(xiàn), PKC、PI3K和NF-κB信號通路參與了LPS誘導CSE表達的過程。糖皮質(zhì)激素(glucocorticoids, GCs)是臨床常用的抗炎抗休克藥物,已有大量資料表明GCs可以抑制體內(nèi)另一種在內(nèi)毒素和感染性休克中發(fā)揮重要作用的內(nèi)源性氣體分子一氧化氮生成以及一氧化氮合成酶的表達,然而GCs對內(nèi)源性H2S的生成有何調(diào)節(jié)作用目前尚不清楚,因此本研究第二部分探討了糖皮質(zhì)激素(地塞米松,DEX)對RAW264.7細胞內(nèi)CSE表達的調(diào)節(jié)作用。結(jié)果顯示,DEX能夠從顯著抑制LPS誘導的CSE mRNA和蛋白表達,并顯著抑制CSE啟動子的轉(zhuǎn)錄激活。
[Abstract]:In mammals, sulfur-containing amino acids can produce endogenous hydrogen sulfide (hydrogen sulfide, H _ 2S) under the catalysis of cystathion-gamma lyase (cystathionine- 緯-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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R363
本文編號：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- 緯-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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R363
【引證文獻】
相關(guān)期刊論文 前1條
1 陳超;高洪;嚴玉霖;陳利平;高利波;趙汝;陳玲;;內(nèi)毒素血癥中肝損傷與H_2S的關(guān)系及陽離子A的保護效應(yīng)分析[J];畜牧獸醫(yī)學報;2011年02期
，本文編號：2417278
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