一氧化碳抑制糖原合酶激酶3β信號傳導(dǎo)改善葡聚糖硫酸鈉誘導(dǎo)結(jié)腸炎
發(fā)布時間：2019-03-04 18:28
【摘要】：題目：一氧化碳抑制糖原合酶激酶3β信號傳導(dǎo)改善葡聚糖硫酸鈉誘導(dǎo)結(jié)腸炎 目的：本實驗主要探討一氧化碳(CO)通過抑制糖原合酶激酶3β (GSK3β)的信號傳導(dǎo)從而改善葡聚糖硫酸鈉(DSS)誘導(dǎo)的急性結(jié)腸炎的機制。 方法：首先將50只7周齡雄性C57BL/6小鼠隨機分為兩批,每一批25只,隨機分為5組,即對照組、DSS組、DSS+CO組、DSS+LiCl組與CO組,每組5只。其中,DSS, DSS+CO以及DSS+LiCl組的小鼠飲用3%DSS,6天后轉(zhuǎn)喂高壓滅菌水。而對照組與CO組始終飲用高壓滅菌水。隨后我們將CO組與DSS+CO組的小鼠放入密閉箱使其吸入250ppm的一氧化碳,每日4小時,而對DSS+LiCl組的小鼠則每日施行腹腔內(nèi)注射氯化鋰(LiCl)200mg/kg。其中對第一批小鼠我們記錄其12天的生存率。而對于第二批小鼠,當(dāng)實驗進行到第10天,我們將小鼠處死并取出結(jié)腸做組織檢查與mRNA和蛋白質(zhì)表達分析。與此同時,從第二批小鼠的腸系膜和脛骨中提取淋巴結(jié)細(xì)胞與骨髓衍生巨噬細(xì)胞(BMMs),分析細(xì)胞中促炎性細(xì)胞因子的mRNA與蛋白質(zhì)表達。在體外,我們主要培育U937人類單核細(xì)胞株與腸系膜淋巴結(jié)細(xì)胞(MLNs)。我們首先用一氧化碳釋放分子2(CORM2)和氯化鋰對這兩種細(xì)胞施行30分鐘的預(yù)處理,隨后通過30分鐘的脂多糖(LPS)刺激分析細(xì)胞中促炎性細(xì)胞因子的mRNA與蛋白質(zhì)的表達。 結(jié)果：在體內(nèi)實驗中,DSS組的小鼠生存率顯著下降,并在結(jié)腸組織,MLNs與BMMs細(xì)胞中促炎性細(xì)胞因子,如：腫瘤壞死因子(TNFα),誘導(dǎo)型一氧化氮合成酶(iNOS)的表達顯著增高。然而通過吸入一氧化碳,TNFα與iNOS的表達顯著減少,并且通過對GSK3β的第9位絲氨酸殘基磷酸化而使其失活。我們通過組織學(xué)檢查也發(fā)現(xiàn)一氧化碳可改善由DSS損傷的結(jié)腸組織。在體外實驗中也發(fā)現(xiàn),CORM2可抑制LPS誘導(dǎo)的促炎性細(xì)胞因子的表達,以及GSK3β的信號傳導(dǎo)。 結(jié)論：通過研究一氧化碳的抗炎作用,我們發(fā)現(xiàn)一氧化碳可抑制GSK3β的活性及其信號傳導(dǎo)從而改善由DSS誘導(dǎo)的急性結(jié)腸炎。并且揭示了一氧化碳對炎癥性腸道疾病具有一定的治療作用。
[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 偽 (TNF 偽) and inducible nitric oxide synthase (iNOS) in colon tissue, MLNs and BMMs cells increased significantly. However, by inhaling carbon monoxide, the expression of TNF 偽 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.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：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 偽 (TNF 偽) and inducible nitric oxide synthase (iNOS) in colon tissue, MLNs and BMMs cells increased significantly. However, by inhaling carbon monoxide, the expression of TNF 偽 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.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R574.62
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