一氧化碳抑制糖原合酶激酶3β信号传导改善葡聚糖硫酸钠诱导结肠炎
发布时间：2019-03-04 18:28
【摘要】：题目：一氧化碳抑制糖原合酶激酶3β信号传导改善葡聚糖硫酸钠诱导结肠炎 目的：本实验主要探讨一氧化碳(CO)通过抑制糖原合酶激酶3β (GSK3β)的信号传导从而改善葡聚糖硫酸钠(DSS)诱导的急性结肠炎的机制。 方法：首先将50只7周龄雄性C57BL/6小鼠随机分为两批,每一批25只,随机分为5组,即对照组、DSS组、DSS+CO组、DSS+LiCl组与CO组,每组5只。其中,DSS, DSS+CO以及DSS+LiCl组的小鼠饮用3%DSS,6天后转喂高压灭菌水。而对照组与CO组始终饮用高压灭菌水。随后我们将CO组与DSS+CO组的小鼠放入密闭箱使其吸入250ppm的一氧化碳,每日4小时,而对DSS+LiCl组的小鼠则每日施行腹腔内注射氯化锂(LiCl)200mg/kg。其中对第一批小鼠我们记录其12天的生存率。而对于第二批小鼠,当实验进行到第10天,我们将小鼠处死并取出结肠做组织检查与mRNA和蛋白质表达分析。与此同时,从第二批小鼠的肠系膜和胫骨中提取淋巴结细胞与骨髓衍生巨噬细胞(BMMs),分析细胞中促炎性细胞因子的mRNA与蛋白质表达。在体外,我们主要培育U937人类单核细胞株与肠系膜淋巴结细胞(MLNs)。我们首先用一氧化碳释放分子2(CORM2)和氯化锂对这两种细胞施行30分钟的预处理,随后通过30分钟的脂多糖(LPS)刺激分析细胞中促炎性细胞因子的mRNA与蛋白质的表达。 结果：在体内实验中,DSS组的小鼠生存率显著下降,并在结肠组织,MLNs与BMMs细胞中促炎性细胞因子,如：肿瘤坏死因子(TNFα),诱导型一氧化氮合成酶(iNOS)的表达显著增高。然而通过吸入一氧化碳,TNFα与iNOS的表达显著减少,并且通过对GSK3β的第9位丝氨酸残基磷酸化而使其失活。我们通过组织学检查也发现一氧化碳可改善由DSS损伤的结肠组织。在体外实验中也发现,CORM2可抑制LPS诱导的促炎性细胞因子的表达,以及GSK3β的信号传导。 结论：通过研究一氧化碳的抗炎作用,我们发现一氧化碳可抑制GSK3β的活性及其信号传导从而改善由DSS诱导的急性结肠炎。并且揭示了一氧化碳对炎症性肠道疾病具有一定的治疗作用。
[Abstract]:Topic: carbon monoxide inhibits the signal transduction of glycogen synthase kinase 3 尾 to improve dextran sulfate-induced colitis objective: to investigate the role of carbon monoxide (CO) in inhibiting the signal of glycogen synthase kinase 3 尾 (GSK3 尾) in rats with colitis induced by sodium dextran sulfate. Conduction thus improves the mechanism of acute colitis induced by sodium dextran sulfate (DSS). Methods: at first, 50 7-week-old male C57BL/6 mice were randomly divided into two groups, each with 25 mice. They were randomly divided into 5 groups: control group, DSS CO group, DSS LiCl group and CO group, with 5 mice in each group. The mice in, DSS, DSS CO and DSS LiCl groups drank 3% DSS and were fed with high pressure sterilized water 6 days later. The control group and CO group always drank high pressure sterilized water. Then we put the mice of CO group and DSS CO group into a closed chamber to inhale carbon monoxide of 250ppm for 4 hours, while the mice of DSS LiCl group received intraperitoneal injection of lithium chloride 200mg / kg 路d ~ (- 1) 路d ~ (- 1). For the first group of mice, we recorded their 12-day survival rate. For the second batch of mice, when the experiment was carried out on the 10th day, we killed the mice and took out the colon for tissue examination and mRNA and protein expression analysis. Meanwhile, (BMMs), was extracted from the mesentery and tibia of the second batch of mice to analyze the expression of pro-inflammatory cytokines (mRNA) and protein in bone marrow-derived macrophages (BMCs). In vitro, we mainly cultured U937 human monocytes and mesenteric lymph node cells (MLNs). We pretreated the two cells with carbon monoxide releasing molecule 2 (CORM2) and lithium chloride for 30 minutes, and then analyzed the expression of pro-inflammatory cytokines mRNA and protein by lipopolysaccharide (LPS) stimulation for 30 minutes. Results: in vivo, the survival rate of mice in DSS group decreased significantly, and the expression of pro-inflammatory cytokines such as tumor necrosis factor 伪 (TNF 伪) and inducible nitric oxide synthase (iNOS) in colon tissue, MLNs and BMMs cells increased significantly. However, by inhaling carbon monoxide, the expression of TNF 伪 and iNOS decreased significantly, and it was inactivated by phosphorylation of serine residue at position 9 of GSK3 尾. We also found that carbon monoxide can improve colon tissue damaged by DSS by histological examination. In vitro, it was also found that CORM2 could inhibit the expression of pro-inflammatory cytokines induced by LPS and the signal transduction of GSK3 尾. Conclusion: by studying the anti-inflammatory effect of carbon monoxide, we found that carbon monoxide can inhibit the activity of GSK3 尾 and its signal transduction, thus improving the acute colitis induced by DSS. It also revealed that carbon monoxide has a certain therapeutic effect on inflammatory intestinal diseases.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62
[Abstract]:Topic: carbon monoxide inhibits the signal transduction of glycogen synthase kinase 3 尾 to improve dextran sulfate-induced colitis objective: to investigate the role of carbon monoxide (CO) in inhibiting the signal of glycogen synthase kinase 3 尾 (GSK3 尾) in rats with colitis induced by sodium dextran sulfate. Conduction thus improves the mechanism of acute colitis induced by sodium dextran sulfate (DSS). Methods: at first, 50 7-week-old male C57BL/6 mice were randomly divided into two groups, each with 25 mice. They were randomly divided into 5 groups: control group, DSS CO group, DSS LiCl group and CO group, with 5 mice in each group. The mice in, DSS, DSS CO and DSS LiCl groups drank 3% DSS and were fed with high pressure sterilized water 6 days later. The control group and CO group always drank high pressure sterilized water. Then we put the mice of CO group and DSS CO group into a closed chamber to inhale carbon monoxide of 250ppm for 4 hours, while the mice of DSS LiCl group received intraperitoneal injection of lithium chloride 200mg / kg 路d ~ (- 1) 路d ~ (- 1). For the first group of mice, we recorded their 12-day survival rate. For the second batch of mice, when the experiment was carried out on the 10th day, we killed the mice and took out the colon for tissue examination and mRNA and protein expression analysis. Meanwhile, (BMMs), was extracted from the mesentery and tibia of the second batch of mice to analyze the expression of pro-inflammatory cytokines (mRNA) and protein in bone marrow-derived macrophages (BMCs). In vitro, we mainly cultured U937 human monocytes and mesenteric lymph node cells (MLNs). We pretreated the two cells with carbon monoxide releasing molecule 2 (CORM2) and lithium chloride for 30 minutes, and then analyzed the expression of pro-inflammatory cytokines mRNA and protein by lipopolysaccharide (LPS) stimulation for 30 minutes. Results: in vivo, the survival rate of mice in DSS group decreased significantly, and the expression of pro-inflammatory cytokines such as tumor necrosis factor 伪 (TNF 伪) and inducible nitric oxide synthase (iNOS) in colon tissue, MLNs and BMMs cells increased significantly. However, by inhaling carbon monoxide, the expression of TNF 伪 and iNOS decreased significantly, and it was inactivated by phosphorylation of serine residue at position 9 of GSK3 尾. We also found that carbon monoxide can improve colon tissue damaged by DSS by histological examination. In vitro, it was also found that CORM2 could inhibit the expression of pro-inflammatory cytokines induced by LPS and the signal transduction of GSK3 尾. Conclusion: by studying the anti-inflammatory effect of carbon monoxide, we found that carbon monoxide can inhibit the activity of GSK3 尾 and its signal transduction, thus improving the acute colitis induced by DSS. It also revealed that carbon monoxide has a certain therapeutic effect on inflammatory intestinal diseases.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62
【相似文献】
相关期刊论文 前10条
1 王群英,陈村龙,王继德,赖卓胜,张亚历,刘荣;葡聚糖硫酸钠致溃疡性结肠炎小鼠模型的建立[J];第一军医大学学报;2002年07期
2 吴小平,刘德良,凌奇荷;酪酸菌对大鼠右旋葡聚糖硫酸钠结肠炎的治疗作用[J];中华消化杂志;2003年05期
3 王兆梅;李琳;李冰;郭祀远;;半合成β-1,4-葡聚糖硫酸钠的抗凝血特性(英文)[J];药学学报;2006年04期
4 舒德忠;万先惠;刘华蓉;杨俊卿;周岐新;;盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究(英文)[J];Journal of Chinese Pharmaceutical Sciences;2006年03期
5 赵翠娟;王承党;;c-Jun氨基末端激酶选择性抑制剂对葡聚糖硫酸钠诱导的小鼠结肠炎的影响[J];世界华人消化杂志;2011年05期
6 吴瑛;汪芳裕;魏娟;朱东海;;甘露糖结合凝集素在小鼠葡聚糖硫酸钠结肠炎发病中的机制研究[J];医学研究生学报;2010年02期
7 韩秋凤;洪小冰;王云芸;刘向东;陈洁;;浒苔多糖对右旋葡聚糖硫酸钠致小鼠溃疡性结肠炎的防治研究[J];海峡预防医学杂志;2010年02期
8 姚安龙;郝献华;龚剑峰;朱维铭;李宁;李秋荣;黎介寿;;小檗碱对葡聚糖硫酸钠所致结肠炎小鼠的肠黏膜组织结构及内质网应激的影响[J];肠外与肠内营养;2011年03期
9 林凯璇;赵晓航;;氧化偶氮甲烷/葡聚糖硫酸钠模型在炎症性肠病和癌形成物质的生物测定运用[J];转化医学杂志;2013年05期
10 李W毲，
本文编号：2434522
本文链接：https://www.wllwen.com/yixuelunwen/xiaohjib/2434522.html
最近更新
教材专著
