人胃溃疡肥大细胞、巨噬细胞的反应
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摘要
为进一步探讨肥大细胞和巨噬细胞在人胃溃疡发病过程中的作用和数量变化，本研究用传统肥大细胞甲苯胺蓝(TB)染色法和免疫组化肥大细胞类胰蛋白酶抗体染色法及巨噬细胞CD_(68)抗体染色法对肥大细胞和巨噬细胞在溃疡病组织中的数量变化及分布进行了研究。结果显示，在对照组和溃疡组，TB染色显示的肥大细胞数量明显少于类胰蛋白酶抗体染色后显示的肥大细胞数量(P＜0.05)，可能是由于标本经甲醛固定后，粘膜肥大细胞不易用TB等常规染色方法显示。在溃疡组，TB染色和类胰蛋白酶抗体染色后，肥大细胞数量明显多于对照组，统计分析显示差异有显著性，(P＜0.05)。以近溃疡底部肥大细胞数量较多，细胞脱颗粒明显。免疫组化CD_(68)抗体染色后，对照组巨噬细胞数量较少，多分布于粘膜层腺体周围结缔组织中。在溃疡组，巨噬细胞数量较对照组显著增加，统计结果显示，(P＜0.05)，以近溃疡底部数量最多，且细胞大小不等，形态不规则。在溃疡周围小血管中可见大量CD_(68)阳性细胞聚集。本研究提示，在胃溃疡组织中，肥大细胞和巨噬细胞数量变化具有相关性，可能肥大细胞和巨噬细胞参与了胃溃疡的发病和发展过程。本文对肥大细胞和巨噬细胞在胃溃疡发病、发展及愈合过程中的作用机理进行了讨论。
In order to further investigate the roles and number changes of mast cells and macrophages during the development of the human stomach ulcer, mast cells were stained with toluidine blue and antibody against tryptase, and antibody against CD68 was used to stain macrophages .The results indicated that the number of mast cells both in control and ulcer groups after staining with antibody against tryptase was significantly greater than that after staining with TB (P<0.05), suggesting that after fixed with formaldehyde, mucosal mast cells could not be stained with traditional methods such as TB staining .In ulcer groups , after staining with TB or antibody against tryptase, the number of mast cells was significantly higher than that in control group (P<0.05). The mast cells were mainly distributed in the area close to the ulcer with obvious degranulation. The results of immuno- staining with CD68 antibody showed that the macrophages in control group were mainly distributed in the connective tissue around the gastric glands, and the number was less than that in the ulcer groups, the macrophages around the ulcer site were irregular in size and had various forms. In the small blood vessel near the ulcer site, a large number of CD68 positive cells were found. The findings
indicated that there was correlation in number between mast cells and macrophages in ulcer tissue. It might be that mast cells and macrophages took part in the process of ulcer formation and development . The significance of mast cells and macrophages in the formation, development and healing of stomach ulcer was discussed.
In order to further investigate the roles and number changes of mast cells and macrophages during the development of the human stomach ulcer, mast cells were stained with toluidine blue and antibody against tryptase, and antibody against CD68 was used to stain macrophages .The results indicated that the number of mast cells both in control and ulcer groups after staining with antibody against tryptase was significantly greater than that after staining with TB (P<0.05), suggesting that after fixed with formaldehyde, mucosal mast cells could not be stained with traditional methods such as TB staining .In ulcer groups , after staining with TB or antibody against tryptase, the number of mast cells was significantly higher than that in control group (P<0.05). The mast cells were mainly distributed in the area close to the ulcer with obvious degranulation. The results of immuno- staining with CD68 antibody showed that the macrophages in control group were mainly distributed in the connective tissue around the gastric glands, and the number was less than that in the ulcer groups, the macrophages around the ulcer site were irregular in size and had various forms. In the small blood vessel near the ulcer site, a large number of CD68 positive cells were found. The findings
indicated that there was correlation in number between mast cells and macrophages in ulcer tissue. It might be that mast cells and macrophages took part in the process of ulcer formation and development . The significance of mast cells and macrophages in the formation, development and healing of stomach ulcer was discussed.
引文
1．杨红，张席锦．大鼠脑内5-羟色胺在应激性溃疡形成中的作用．生理学报，1985：37：416-424．
2. Cho CH, Koo MW, Garg GP et al. Stress-induced gastric ulceration: Its aetiology and clinical implieations. Scand J Gastroenterol,1992;27: 257-262.
3. Ogle CW, Hui SC. The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats. Experientia,1995; 51:786-789.
4. Enerbaek L. Mast cells in rat gastrointestinal mueosa:Ⅰ.Effects of fixation. Aeta Path Mierobiol Scand, 1966; 66:289—302.
5. Enerbaek L. Mast cells in rat gastrointestinal mucosa:Ⅱ Dye binding and metachromatic properties. Acta Path Mierobiol Scand, 1966;66:303—312.
6. Wingren U, Enerbaek L.Mueosal mast cells of the rat intestine: A re-evaluation of fixation and staining properties with special reference to protein blocking and solubility of the granular glyeosaminoglyean. Histoehem J, 1983;15: 571-582.
7. Shanahan F, Denburg JA, Fox J et al. Mast cell heterogeneity: Effects of neuroenteric peptides on histamine release. J Immunol, 1985;135:1331-1337.
8. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiological Reviews, 1997;77:1033-1079.
9. Strobel S. Human intestinal mucosal mast cells: Evaluation of fixation and staining techniques. J Clin Path, 1981; 34:851.
10. Ruitenberg FJ. Effect of fixation on the light microscopical visualization of mast cells in the mucosa and connective tissue of the human duodenum. Int Archs Allergy Appl Immun,1982;67:233.
11．陈晓军，何泽涌．不同固定液染色法显示结缔组织肥大细胞效果的比较．解剖学杂志，1992；15：287．
12．高崇，何泽涌．肥大细胞与其它结缔组织细胞在光镜下同时显示法的研究．山西医学院学报，1989；20：206-210．
13．景雅，薛润梅，张中英等．宫颈鳞癌间质肥大细胞的组化特征．山西医药杂志，1991：20：71．
14．王周南，李光．肥大细胞的异质性与疾病．国外医学生理病理科学与临床分册，1990；10：137-140．
15．陈立红，钱峰，余心如．溃疡病胃壁内肥大细胞的观察临床与实验病理学杂志，1995；11：292-294．
16. Malaviya R, Abraham SN. Clinical implications of mast cell-bacteria interaction. J Mol Med, 1998;76:617-623.
17. Yasuhiro T, Konaka A, Kate S et al. Gastric mucosal damage induced by compound 48/80: Roles of serotonin and nitric oxide. J Gastroenterol Hepatol, 1998;13:1081—1083.
18. Kobayashi T, ohta Y, Yoshino J. Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80. Eur J Pharmacol, 2001;414:271—279.
19. Ohta Y, Kobayashi T, Ishiguro I. Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast cell degranulator. Pharmacol Res, 1999;39:261-267.
20. Brown JK, Jones CA, Rooney LA et al. Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. Am J physiol Lung cell Mol Physiol, 2002;282:197-206.
21．袁孝宾，孙琰，王梓祯．肥大细胞的新概念．国外医学生理病理科学与临床分册，1994；14：93-95．
22. Sommerhoff CP. Mast cell tryptases and airway remodeling. Am J Respir Crit care Med, 2001;164:52-58.
23．成令忠主编．组织学．第二版．北京：人民卫生出版社出版，1994；P238．
24. Nakajima S, Arizono N, Hattori T et al. Increase in mucosal and connective tissue-type mast cells in the stomach with acetic acid-induced ulcer in rat. APMIS, 1996;104:19-29.
25. Huang XR, Chun Hui CW, Chen YX et al. Macrophage migration inhibitory factor is an important mediator in the pathogenesis of
gastric inflammation in rats. Gastroenterology, 2001;121:619-630.
26．刘彦，崔肇春．巨噬细胞的激活与其信息传递．国外医学免疫学分册，1996；16：214-217．
27．罗高兴，徐秋萍，彭代智等．一氧化氮的免疫调节作用．上海免疫学杂志，1996；16：245-247．
28．郑永晨，杨贵贞．一氧化氮与巨噬细胞的免疫调节．国外医学免疫学分册，1995；16：204-206．
29. Kobayashi N, Kataoka T, Tsukimi Y et al. Role of p38 mitogen-activated protein kinase in the healing of gastric ulcers in rats. J Physiol Pharmacol,2001;52:195-210.
30. Qiu BS, Pfeiffer CJ, Cho CH. Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. Digestion, 1996;57:60-66.
31．陈吉，韩亚京．活动期溃疡性结肠炎与一氧化氮关系的临床研究．中华消化杂志，1998；18：295-297．
2. Cho CH, Koo MW, Garg GP et al. Stress-induced gastric ulceration: Its aetiology and clinical implieations. Scand J Gastroenterol,1992;27: 257-262.
3. Ogle CW, Hui SC. The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats. Experientia,1995; 51:786-789.
4. Enerbaek L. Mast cells in rat gastrointestinal mueosa:Ⅰ.Effects of fixation. Aeta Path Mierobiol Scand, 1966; 66:289—302.
5. Enerbaek L. Mast cells in rat gastrointestinal mucosa:Ⅱ Dye binding and metachromatic properties. Acta Path Mierobiol Scand, 1966;66:303—312.
6. Wingren U, Enerbaek L.Mueosal mast cells of the rat intestine: A re-evaluation of fixation and staining properties with special reference to protein blocking and solubility of the granular glyeosaminoglyean. Histoehem J, 1983;15: 571-582.
7. Shanahan F, Denburg JA, Fox J et al. Mast cell heterogeneity: Effects of neuroenteric peptides on histamine release. J Immunol, 1985;135:1331-1337.
8. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiological Reviews, 1997;77:1033-1079.
9. Strobel S. Human intestinal mucosal mast cells: Evaluation of fixation and staining techniques. J Clin Path, 1981; 34:851.
10. Ruitenberg FJ. Effect of fixation on the light microscopical visualization of mast cells in the mucosa and connective tissue of the human duodenum. Int Archs Allergy Appl Immun,1982;67:233.
11．陈晓军，何泽涌．不同固定液染色法显示结缔组织肥大细胞效果的比较．解剖学杂志，1992；15：287．
12．高崇，何泽涌．肥大细胞与其它结缔组织细胞在光镜下同时显示法的研究．山西医学院学报，1989；20：206-210．
13．景雅，薛润梅，张中英等．宫颈鳞癌间质肥大细胞的组化特征．山西医药杂志，1991：20：71．
14．王周南，李光．肥大细胞的异质性与疾病．国外医学生理病理科学与临床分册，1990；10：137-140．
15．陈立红，钱峰，余心如．溃疡病胃壁内肥大细胞的观察临床与实验病理学杂志，1995；11：292-294．
16. Malaviya R, Abraham SN. Clinical implications of mast cell-bacteria interaction. J Mol Med, 1998;76:617-623.
17. Yasuhiro T, Konaka A, Kate S et al. Gastric mucosal damage induced by compound 48/80: Roles of serotonin and nitric oxide. J Gastroenterol Hepatol, 1998;13:1081—1083.
18. Kobayashi T, ohta Y, Yoshino J. Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80. Eur J Pharmacol, 2001;414:271—279.
19. Ohta Y, Kobayashi T, Ishiguro I. Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast cell degranulator. Pharmacol Res, 1999;39:261-267.
20. Brown JK, Jones CA, Rooney LA et al. Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. Am J physiol Lung cell Mol Physiol, 2002;282:197-206.
21．袁孝宾，孙琰，王梓祯．肥大细胞的新概念．国外医学生理病理科学与临床分册，1994；14：93-95．
22. Sommerhoff CP. Mast cell tryptases and airway remodeling. Am J Respir Crit care Med, 2001;164:52-58.
23．成令忠主编．组织学．第二版．北京：人民卫生出版社出版，1994；P238．
24. Nakajima S, Arizono N, Hattori T et al. Increase in mucosal and connective tissue-type mast cells in the stomach with acetic acid-induced ulcer in rat. APMIS, 1996;104:19-29.
25. Huang XR, Chun Hui CW, Chen YX et al. Macrophage migration inhibitory factor is an important mediator in the pathogenesis of
gastric inflammation in rats. Gastroenterology, 2001;121:619-630.
26．刘彦，崔肇春．巨噬细胞的激活与其信息传递．国外医学免疫学分册，1996；16：214-217．
27．罗高兴，徐秋萍，彭代智等．一氧化氮的免疫调节作用．上海免疫学杂志，1996；16：245-247．
28．郑永晨，杨贵贞．一氧化氮与巨噬细胞的免疫调节．国外医学免疫学分册，1995；16：204-206．
29. Kobayashi N, Kataoka T, Tsukimi Y et al. Role of p38 mitogen-activated protein kinase in the healing of gastric ulcers in rats. J Physiol Pharmacol,2001;52:195-210.
30. Qiu BS, Pfeiffer CJ, Cho CH. Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. Digestion, 1996;57:60-66.
31．陈吉，韩亚京．活动期溃疡性结肠炎与一氧化氮关系的临床研究．中华消化杂志，1998；18：295-297．
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