GSH在DSS诱导的小鼠实验性肠炎中的作用
张静, 中国人民解放军总医院军医进修学院 北京市 100853
韩英, 纪欣, 王志红, 李虹义, 郑力, 北京军区总医院消化内科 北京市 100700
张静, 女,1973-05-02生, 河北保定人, 汉族.1997年承德医学院本科毕业, 解放军总医院军医进修学院2002级硕士研究生, 主治医师, 主要从事炎症性肠病的发病及免疫机制等方面的研究.
北京市自然科学基金资助项目, No. 7042064
通讯作者: 韩英,100853, 北京市东城区南门仓5号, 北京军区总医院消化内科.
电话: 010-66721009
, 百拇医药
收稿日期: 2005-04-11 接受日期: 2005-04-27
Roles of Glutathione in dextran sodium sulphate-induced colitis in mice
Jing Zhang, Ying Han, Xin Ji, Zhi-Hong Wang, Hong-Yi Li, Li Zheng
Jing Zhang, Postgraduate Medical School, General Hospital of Chinese PLA, Beijing 100853, China
Ying Han, Xin Ji, Zhi-Hong Wang, Hong-Yi Li, Li Zheng, Department of Gastroenterology, General Hospital of Beijing Military Command, Beijing 100700, China
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Supported by the Natural Science Foundation of Beijing, China, No.7042064
Correspondence to: Dr. Ying Han, Department of Gastroenterology, General Hospital of Beijing Military Command, 5 Nanmencang, East District, Beijing 100700, China.
Received: 2005-04-11 Accepted: 2005-04-27
Abstract
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AIM: To investigate the expression of glutathione (GSH) in dextran sodium sulphate(DSS)-induced colitic mucosa and its relationship with cytokine secretion as well as mucosal injury.
METHODS: BALB/c mice in DSS group (n = 10) were fed with 50 g/L DSS to induce experimental colitis and those in normal controls (n = 10) were fed with distilled water. All the mice were killed after 7 days. The pathological changes of the colonic tissues were examined while immunohi-stochemstry was performed with GSH1 antibody to determine the GSH expression. ELISA was used to detect the expression of IL-4 and IFN-g.
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RESULTS: The manifestations of acute colitis such as weight decrease, diarrhea and bloody stool appeared in mice of DSS group. focal crypt lesionsPathologically, focal crypt distortion, granulocyte and macrophage invasion were observed. The level of GSH in DSS group was significantly lower than that in control group (20.6 vs 3.14±1.0, t = 3.95, P = 0.01), whereas the expression of IL-4 was marked higher (38.7±4.7 vs 28.7±6.7, t = 3.16, P = 0.009). The content of IFN-g was decreased in DSS group (P>0.05).
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CONCLUSION: Low expression of GSH is related to the increase of IL-4, decrease of IFN-g and mucosal injury in DSS-induced colitis in mice.
Key Words: Glutathione; Dextran sodium sulphate; Colitis; Mice; IL-4; IFN-g; Mucosal injury
Zhang J, Han Y, Ji X, Wang ZH, Li HY, Zheng L. Roles of Glutathione in dextran sodium sulphate-induced colitis in mice. Shijie Huaren Xiaohua Zazhi 2005;13(12):1400-1403
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摘要
目的: 探讨硫酸葡聚糖钠(dextran sodium sulphate，DSS)诱导的小鼠肠炎模型病变结肠组织的谷胱甘肽(GSH)变化及其与病变组织分泌的Th1/Th2型细胞因子IFN-g,IL-4及黏膜损伤的关系.
方法: 实验组小鼠(n = 10)给予含50 g/L DSS的蒸馏水自由饮用7 d之后处死，分离出的病变结肠一部分评价其病理学改变并用GSH1抗体做免疫组化，另一部分结肠培养后检测其IL-4、IFN-g的表达.对照组小鼠(n= 10)给予蒸馏水自由饮用7 d之后处死.
结果: DSS诱导实验性肠炎小鼠口服50 g/L的DSS溶液7 d出现体重减轻、腹泻、血便等急性肠炎的表现.病理学切片HE染色发现小鼠病变结肠腺体结构紊乱，黏膜和黏膜下单核细胞和多核细胞浸润.DSS组病变肠段组织GSH表达较对照组明显减少(2±0.6 vs 3.14±1.0，t = 3.95, P = 0.01<0.05)，病变结肠分泌的IL-4明显升高(38.7±4.7 vs 28.7±6.7，t = 3.16, P = 0.009<0.01)， IFN-g轻度降低(P>0.05).
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结论: DSS诱导的实验性肠炎小鼠病变结肠组织GSH的减少与病变结肠组织分泌的细胞因子IL-4增加、IFN-g下降以及黏膜损伤相关.
关键词: 谷胱甘肽; 硫酸葡聚糖钠; 肠炎; 小鼠; IL-4; IFN-g;黏膜损伤
张静, 韩英, 纪欣, 王志红, 李虹义, 郑力. GSH在DSS诱导的小鼠实验性肠炎中的作用. 世界华人消化杂志 2005;13(12):1400-1403:对照组;B:实验组.
图2 对照组和实验组小鼠结肠组织GSH的表达(×100).A:对照组;B:实验组.
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3 讨论
DSS诱导的BALB/c小鼠急性实验性肠炎模型表现为体重减轻，腹泻，血便等.病理学检查发现小鼠左半结肠病变较右半结肠为重，结肠黏膜腺体结构紊乱，单核细胞和多核细胞浸润，黏膜局部糜烂，部分隐窝破坏等[6-7].IBD患者的胃肠道炎症中渗透的大量炎症细胞包括巨噬细胞和中性粒细胞等通过产生反应性氧簇(reactiveoxygen species，ROS)而将炎症肠道暴露于氧化应激中.而胃肠道黏膜自身有一些抗氧化防御系统，可以通过中和连续生成的ROS抵消其损害的影响.在这些防御网络中，内生硫氢基团，主要是还原型谷胱甘肽(GSH)起着重要的作用.GSH是一种包含一个巯基的非蛋白三肽，GSH大量存在于各种不同细胞中在多种生化过程中起着重要的作用.GSH构成细胞防御氧化损伤机制中的第一道防线，而且是普遍存在的细胞类型中的主要氧化还原缓冲剂.在其众多功能中，其含半胱氨酸的三肽可以减轻蛋白质的二硫化，减轻自由基和内毒素的毒性作用，并维持细胞内氧化还原的平衡[8].Sidoet al[4]的研究发现与健康对照组比较IBD患者半胱氨酸浓度明显减少，其减低水平与疾病临床活动指数相关，去蛋白血浆中总的巯基成分均明显减少，术后3mo恢复到正常水平.Zea-Iriarteet al[9]发现在TNS(三硝基苯硫酸，trinitrobenzenesulphonic acid)诱导的实验性肠炎中，GSH浓度及谷胱甘肽硫基转移酶，Cu，Zn超氧化物歧化酶均减低，但是谷胱甘肽过氧化物酶却增加.我们的实验研究发现DSS组病变肠段组织GSH表达明显低于对照组(2±0.6vs 3.14±1.0，t= 3.95，P= 0.01<0.05)，与文献报告相似，说明GSH不足与IBD和实验性肠炎的炎症相关，削弱黏膜的抗氧化能力可能会促进肠道的氧化损伤.
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Th1和Th2细胞因子反应类型对于小鼠炎症和感染的慢性化和侵袭性可产生影响，是慢性肠道炎症重要的决定因素.Th1/Th2型反应平衡是由分泌细胞因子的类型决定的.Th1型是以通过伴随抗原提呈细胞(APC)生成的IL-12而产生IFN-g为特征.Th2型则是以低IFN-g/高IL-4和低IFN-g/高IL-10为特征[10].本实验中DSS诱导的实验性肠炎小鼠病变肠段分泌的IL-4明显增加，IFN-g下降，致IL-4/IFN-g显著升高，说明DSS诱导的急性实验性肠炎是以Th2型免疫反应为主的炎性改变.Petersonet al[11]和Murataet al[12]曾报道鼠的抗原提呈细胞(APC)或腹腔定居的巨噬细胞中GSH的损耗可使IL-12的分泌减少并导致典型的Th1细胞因子形式向Th2反应模式转化.Petersonet al[11]的研究还显示应用GSH损耗或补充药物时巨噬细胞内GSH的水平可以影响Th1/Th2细胞因子的倾向.且将来源于GSH损耗小鼠的T细胞与未处理的BALB/C鼠的巨噬细胞一起培养可产生正常量的IFN-g，因此IFN-g产量减少是由于巨噬细胞而不是T细胞中GSH损耗造成的.另外Jeanninet al[13]在研究易于产生IL-4的培养细胞系统中发现在培养液中增加GSH的水平可使IL-4的产量以量效依赖的方式减低.这些研究结果充分表明巨噬细胞内的GSH水平对于调节在免疫反应中向Th1或Th2细胞因子反应的发展趋势具有重要的作用.
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总之，本研究结果显示DSS诱导的急性实验性肠炎小鼠病变结肠的组织GSH的减少与病变结肠组织分泌的细胞因子IL-4增加、IFN-g减低及结肠黏膜损伤有相关性，但是其机理不明.GSH的表达有可能影响不同类型炎性细胞因子的分泌进而影响黏膜组织的损伤.同时提示肠道黏膜免疫异常在IBD发病机制中的作用不容忽视，特别是巨噬细胞中的GSH的变化是否与黏膜炎症损伤及Th1/Th2细胞因子分泌的相关性有待于探讨.
4 参考文献
1 Goldin E, Ardite E, Elizalde JI, Odriozola A, Panes J, Pique JM,Fernandez-Checa JC. Gastric mucosal damage
in experimental diabetes in rats: role ofendogenous glutathione. Gastroenterology 1997;112:855-863
, 百拇医药
2 Takeuchi K, Okada M, Ueshima K, Ohuchi T, Okabe S. Endogenoussulfhydryls in healing gastric mucosal
injury induced by HCl in the rat. Digestion 1993;54:91-97
3 Holmes EW, Yong SL, Eiznhamer D, Keshavarzian A. Glutathionecontent of colonic mucosa: evidence for oxidative
damage in active ulcerative colitis. DigDis Sci 1998;43:1088-1095
4 Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W.Impairment of intestinal glutathione synthesis in patients
, http://www.100md.com
with inflammatory bowel disease. Gut 1998;42:485-492
5 Loher F, Schmall K, Freytag P, Landauer N, Hallwachs R, Bauer C,Siegmund B, Rieder F, Lehr HA, Dauer M, Kapp
JF, Endres S, Eigler A. The specific type-4phosphodiesterase inhibitor mesopram alleviates experimental colitis inmice.
J Pharmacol Exp Ther 2003;305:549-556
6 Konrad A, Mahler M, Flogerzi B, Kalousek MB, Lange J, Varga L,Seibold F. Amelioration of murine colitis by feeding
, 百拇医药
a solution of lysed Escherichia coli. ScandJ Gastroenterol 2003;38:172-179
7 Villegas I, Alarcon de la Lastra C, Orjales A, La Casa C. A newflavonoid derivative, dosmalfate, attenuates
the development of dextran sulphatesodium-induced colitis in mice. Int Immunopharmacol 2003;3:1731-1741
8 Murata Y, Amao M, Yoneda J, Hamuro J. Intracellular thiol redoxstatus of macrophages directs the Th1 skewing
, 百拇医药
in thioredoxin transgenic mice duringaging. Mol Immunol 2002;38:747-757
9 Zea-Iriarte WL, Makiyama K, Goto S, Murase K, Urata Y, Sekine I,Hara K, Kondo T. Impairment of antioxidants in
colonic epithelial cells isolated fromtrinitrobenzene sulphonic acid-induced colitis rats. Protective effect of
rebamipide. Scand J Gastroenterol 1996;31:985-992
10 Romagnani P, Annunziato F, Piccinni MP, Maggi E, Romagnani S.Th1/Th2 cells, their associated molecules and role
, 百拇医药
in pathophysiology. Eur CytokineNetw 2000;11:510-511
11 Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathionelevels in antigen-presenting cells modulate
Th1 versus Th2 response patterns. ProcNatl Acad Sci USA 1998;95:3071-3076
12 Murata Y, Ohteki T, Koyasu S, Hamuro J. IFN-gamma andpro-inflammatory cytokine production by
antigen-presenting cells is dictatedby intracellular thiol redox status regulated by oxygen tension. Eur J
Immunol 2002;32:2866-2873
13 Jeannin P, Delneste Y, Aubry JP, Lecoanet-Henchoz S, Gauchat JF,Life P, Bonnefoy JY. Thiols decrease human
IL-4 production and IL-4-inducedimmunoglobulin synthesis. Int Arch Allergy Immunol 1997;113:329-330
编辑 潘伯荣 审读 张海宁, http://www.100md.com( 张 静, 韩 英, 纪 欣, 王志红, 李虹义, 郑 力)
韩英, 纪欣, 王志红, 李虹义, 郑力, 北京军区总医院消化内科 北京市 100700
张静, 女,1973-05-02生, 河北保定人, 汉族.1997年承德医学院本科毕业, 解放军总医院军医进修学院2002级硕士研究生, 主治医师, 主要从事炎症性肠病的发病及免疫机制等方面的研究.
北京市自然科学基金资助项目, No. 7042064
通讯作者: 韩英,100853, 北京市东城区南门仓5号, 北京军区总医院消化内科.
电话: 010-66721009
, 百拇医药
收稿日期: 2005-04-11 接受日期: 2005-04-27
Roles of Glutathione in dextran sodium sulphate-induced colitis in mice
Jing Zhang, Ying Han, Xin Ji, Zhi-Hong Wang, Hong-Yi Li, Li Zheng
Jing Zhang, Postgraduate Medical School, General Hospital of Chinese PLA, Beijing 100853, China
Ying Han, Xin Ji, Zhi-Hong Wang, Hong-Yi Li, Li Zheng, Department of Gastroenterology, General Hospital of Beijing Military Command, Beijing 100700, China
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Supported by the Natural Science Foundation of Beijing, China, No.7042064
Correspondence to: Dr. Ying Han, Department of Gastroenterology, General Hospital of Beijing Military Command, 5 Nanmencang, East District, Beijing 100700, China.
Received: 2005-04-11 Accepted: 2005-04-27
Abstract
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AIM: To investigate the expression of glutathione (GSH) in dextran sodium sulphate(DSS)-induced colitic mucosa and its relationship with cytokine secretion as well as mucosal injury.
METHODS: BALB/c mice in DSS group (n = 10) were fed with 50 g/L DSS to induce experimental colitis and those in normal controls (n = 10) were fed with distilled water. All the mice were killed after 7 days. The pathological changes of the colonic tissues were examined while immunohi-stochemstry was performed with GSH1 antibody to determine the GSH expression. ELISA was used to detect the expression of IL-4 and IFN-g.
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RESULTS: The manifestations of acute colitis such as weight decrease, diarrhea and bloody stool appeared in mice of DSS group. focal crypt lesionsPathologically, focal crypt distortion, granulocyte and macrophage invasion were observed. The level of GSH in DSS group was significantly lower than that in control group (20.6 vs 3.14±1.0, t = 3.95, P = 0.01), whereas the expression of IL-4 was marked higher (38.7±4.7 vs 28.7±6.7, t = 3.16, P = 0.009). The content of IFN-g was decreased in DSS group (P>0.05).
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CONCLUSION: Low expression of GSH is related to the increase of IL-4, decrease of IFN-g and mucosal injury in DSS-induced colitis in mice.
Key Words: Glutathione; Dextran sodium sulphate; Colitis; Mice; IL-4; IFN-g; Mucosal injury
Zhang J, Han Y, Ji X, Wang ZH, Li HY, Zheng L. Roles of Glutathione in dextran sodium sulphate-induced colitis in mice. Shijie Huaren Xiaohua Zazhi 2005;13(12):1400-1403
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摘要
目的: 探讨硫酸葡聚糖钠(dextran sodium sulphate，DSS)诱导的小鼠肠炎模型病变结肠组织的谷胱甘肽(GSH)变化及其与病变组织分泌的Th1/Th2型细胞因子IFN-g,IL-4及黏膜损伤的关系.
方法: 实验组小鼠(n = 10)给予含50 g/L DSS的蒸馏水自由饮用7 d之后处死，分离出的病变结肠一部分评价其病理学改变并用GSH1抗体做免疫组化，另一部分结肠培养后检测其IL-4、IFN-g的表达.对照组小鼠(n= 10)给予蒸馏水自由饮用7 d之后处死.
结果: DSS诱导实验性肠炎小鼠口服50 g/L的DSS溶液7 d出现体重减轻、腹泻、血便等急性肠炎的表现.病理学切片HE染色发现小鼠病变结肠腺体结构紊乱，黏膜和黏膜下单核细胞和多核细胞浸润.DSS组病变肠段组织GSH表达较对照组明显减少(2±0.6 vs 3.14±1.0，t = 3.95, P = 0.01<0.05)，病变结肠分泌的IL-4明显升高(38.7±4.7 vs 28.7±6.7，t = 3.16, P = 0.009<0.01)， IFN-g轻度降低(P>0.05).
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结论: DSS诱导的实验性肠炎小鼠病变结肠组织GSH的减少与病变结肠组织分泌的细胞因子IL-4增加、IFN-g下降以及黏膜损伤相关.
关键词: 谷胱甘肽; 硫酸葡聚糖钠; 肠炎; 小鼠; IL-4; IFN-g;黏膜损伤
张静, 韩英, 纪欣, 王志红, 李虹义, 郑力. GSH在DSS诱导的小鼠实验性肠炎中的作用. 世界华人消化杂志 2005;13(12):1400-1403:对照组;B:实验组.
图2 对照组和实验组小鼠结肠组织GSH的表达(×100).A:对照组;B:实验组.
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3 讨论
DSS诱导的BALB/c小鼠急性实验性肠炎模型表现为体重减轻，腹泻，血便等.病理学检查发现小鼠左半结肠病变较右半结肠为重，结肠黏膜腺体结构紊乱，单核细胞和多核细胞浸润，黏膜局部糜烂，部分隐窝破坏等[6-7].IBD患者的胃肠道炎症中渗透的大量炎症细胞包括巨噬细胞和中性粒细胞等通过产生反应性氧簇(reactiveoxygen species，ROS)而将炎症肠道暴露于氧化应激中.而胃肠道黏膜自身有一些抗氧化防御系统，可以通过中和连续生成的ROS抵消其损害的影响.在这些防御网络中，内生硫氢基团，主要是还原型谷胱甘肽(GSH)起着重要的作用.GSH是一种包含一个巯基的非蛋白三肽，GSH大量存在于各种不同细胞中在多种生化过程中起着重要的作用.GSH构成细胞防御氧化损伤机制中的第一道防线，而且是普遍存在的细胞类型中的主要氧化还原缓冲剂.在其众多功能中，其含半胱氨酸的三肽可以减轻蛋白质的二硫化，减轻自由基和内毒素的毒性作用，并维持细胞内氧化还原的平衡[8].Sidoet al[4]的研究发现与健康对照组比较IBD患者半胱氨酸浓度明显减少，其减低水平与疾病临床活动指数相关，去蛋白血浆中总的巯基成分均明显减少，术后3mo恢复到正常水平.Zea-Iriarteet al[9]发现在TNS(三硝基苯硫酸，trinitrobenzenesulphonic acid)诱导的实验性肠炎中，GSH浓度及谷胱甘肽硫基转移酶，Cu，Zn超氧化物歧化酶均减低，但是谷胱甘肽过氧化物酶却增加.我们的实验研究发现DSS组病变肠段组织GSH表达明显低于对照组(2±0.6vs 3.14±1.0，t= 3.95，P= 0.01<0.05)，与文献报告相似，说明GSH不足与IBD和实验性肠炎的炎症相关，削弱黏膜的抗氧化能力可能会促进肠道的氧化损伤.
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Th1和Th2细胞因子反应类型对于小鼠炎症和感染的慢性化和侵袭性可产生影响，是慢性肠道炎症重要的决定因素.Th1/Th2型反应平衡是由分泌细胞因子的类型决定的.Th1型是以通过伴随抗原提呈细胞(APC)生成的IL-12而产生IFN-g为特征.Th2型则是以低IFN-g/高IL-4和低IFN-g/高IL-10为特征[10].本实验中DSS诱导的实验性肠炎小鼠病变肠段分泌的IL-4明显增加，IFN-g下降，致IL-4/IFN-g显著升高，说明DSS诱导的急性实验性肠炎是以Th2型免疫反应为主的炎性改变.Petersonet al[11]和Murataet al[12]曾报道鼠的抗原提呈细胞(APC)或腹腔定居的巨噬细胞中GSH的损耗可使IL-12的分泌减少并导致典型的Th1细胞因子形式向Th2反应模式转化.Petersonet al[11]的研究还显示应用GSH损耗或补充药物时巨噬细胞内GSH的水平可以影响Th1/Th2细胞因子的倾向.且将来源于GSH损耗小鼠的T细胞与未处理的BALB/C鼠的巨噬细胞一起培养可产生正常量的IFN-g，因此IFN-g产量减少是由于巨噬细胞而不是T细胞中GSH损耗造成的.另外Jeanninet al[13]在研究易于产生IL-4的培养细胞系统中发现在培养液中增加GSH的水平可使IL-4的产量以量效依赖的方式减低.这些研究结果充分表明巨噬细胞内的GSH水平对于调节在免疫反应中向Th1或Th2细胞因子反应的发展趋势具有重要的作用.
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总之，本研究结果显示DSS诱导的急性实验性肠炎小鼠病变结肠的组织GSH的减少与病变结肠组织分泌的细胞因子IL-4增加、IFN-g减低及结肠黏膜损伤有相关性，但是其机理不明.GSH的表达有可能影响不同类型炎性细胞因子的分泌进而影响黏膜组织的损伤.同时提示肠道黏膜免疫异常在IBD发病机制中的作用不容忽视，特别是巨噬细胞中的GSH的变化是否与黏膜炎症损伤及Th1/Th2细胞因子分泌的相关性有待于探讨.
4 参考文献
1 Goldin E, Ardite E, Elizalde JI, Odriozola A, Panes J, Pique JM,Fernandez-Checa JC. Gastric mucosal damage
in experimental diabetes in rats: role ofendogenous glutathione. Gastroenterology 1997;112:855-863
, 百拇医药
2 Takeuchi K, Okada M, Ueshima K, Ohuchi T, Okabe S. Endogenoussulfhydryls in healing gastric mucosal
injury induced by HCl in the rat. Digestion 1993;54:91-97
3 Holmes EW, Yong SL, Eiznhamer D, Keshavarzian A. Glutathionecontent of colonic mucosa: evidence for oxidative
damage in active ulcerative colitis. DigDis Sci 1998;43:1088-1095
4 Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W.Impairment of intestinal glutathione synthesis in patients
, http://www.100md.com
with inflammatory bowel disease. Gut 1998;42:485-492
5 Loher F, Schmall K, Freytag P, Landauer N, Hallwachs R, Bauer C,Siegmund B, Rieder F, Lehr HA, Dauer M, Kapp
JF, Endres S, Eigler A. The specific type-4phosphodiesterase inhibitor mesopram alleviates experimental colitis inmice.
J Pharmacol Exp Ther 2003;305:549-556
6 Konrad A, Mahler M, Flogerzi B, Kalousek MB, Lange J, Varga L,Seibold F. Amelioration of murine colitis by feeding
, 百拇医药
a solution of lysed Escherichia coli. ScandJ Gastroenterol 2003;38:172-179
7 Villegas I, Alarcon de la Lastra C, Orjales A, La Casa C. A newflavonoid derivative, dosmalfate, attenuates
the development of dextran sulphatesodium-induced colitis in mice. Int Immunopharmacol 2003;3:1731-1741
8 Murata Y, Amao M, Yoneda J, Hamuro J. Intracellular thiol redoxstatus of macrophages directs the Th1 skewing
, 百拇医药
in thioredoxin transgenic mice duringaging. Mol Immunol 2002;38:747-757
9 Zea-Iriarte WL, Makiyama K, Goto S, Murase K, Urata Y, Sekine I,Hara K, Kondo T. Impairment of antioxidants in
colonic epithelial cells isolated fromtrinitrobenzene sulphonic acid-induced colitis rats. Protective effect of
rebamipide. Scand J Gastroenterol 1996;31:985-992
10 Romagnani P, Annunziato F, Piccinni MP, Maggi E, Romagnani S.Th1/Th2 cells, their associated molecules and role
, 百拇医药
in pathophysiology. Eur CytokineNetw 2000;11:510-511
11 Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathionelevels in antigen-presenting cells modulate
Th1 versus Th2 response patterns. ProcNatl Acad Sci USA 1998;95:3071-3076
12 Murata Y, Ohteki T, Koyasu S, Hamuro J. IFN-gamma andpro-inflammatory cytokine production by
antigen-presenting cells is dictatedby intracellular thiol redox status regulated by oxygen tension. Eur J
Immunol 2002;32:2866-2873
13 Jeannin P, Delneste Y, Aubry JP, Lecoanet-Henchoz S, Gauchat JF,Life P, Bonnefoy JY. Thiols decrease human
IL-4 production and IL-4-inducedimmunoglobulin synthesis. Int Arch Allergy Immunol 1997;113:329-330
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