UC D S S Wako t 5000 Total sulfur % ES-2030 DSS UC 2 % DSS S E M S N 90 1 % DSS UC Scanning Electron Microscopy

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1 FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFF Vol. 31, pp., 2003 FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFF Ulcerative colitis UC U C 8 BALB/C 2 % Dextran Sodium Sulfate DSS 14 UC 1 % DSS 90 UC UC UC Dextran Sodium Sulfate U C C r o h n 1 ) ~ 6 ) UC 8 BALB/C C a r r a g e e n a n 6 ) ~ 10 ) D S S 6), 11)~27) 1 DSS U C UC [ % 1 Scanning Electron Microscope S E M / 1 50 ]

2 UC D S S Wako t 5000 Total sulfur % ES-2030 DSS UC 2 % DSS S E M S N 90 1 % DSS UC Scanning Electron Microscopy cm h e m a t o x y l i n - e o s i n H E 1) SEM 4 SEM 9 1 % DSS 21 ph M 0.1 M 40 2) B 2210 J - D T H 4 2 k H z % g 1 % DSS mm % g 90 1 % % 70 % 80 % 3 90 % 100 % % t % t 2 E Mann-Whitney 2 2 Mann-Whitney Fig. 1 1) 90 66

3 Fig.1. The change of body weight by intake of diluted DSS solution: Dotted line denotes control group, Straight line denotes experiment group. N denotes sample number, and the bar means the range of average SD. (NS: not significant, **: p 0.01, *: p 0.05) Fig. 2. The change of colorectal length. : Dotted line denotes control group, Straight line denotes experiment group. N denotes sample number of experimental group and the bar means the range of average SD. The symbol **means statistical significance (p 0.01) by Mann-Whitney test, using the whole dates of experimental group (n=48) and control group (n=14). 14 n = 56 n = 14 M a n n - 3 Whitney p Fig. 2 67

4 Fig. 3,. Histological figure of rectum of a normal mouse. Fig. 4,. Histological figure of rectum of experimental mice on the 3rd day. Histological examination reveals lymphoectasia (arrow in mucosal layer. Fig. 5,. Histological figure of rectum of experimental mice on the 7th day. Erosion (arrow) is seen in Fig.5 and desquamation of crypt (arrow) in Fig.5. 2) UC 7 1 cm a b Fig. 5a, 21 Fig. 3a, b DSS 3 Fig. 4a, b 14 7 F i g. 6a, b Fig. 7a, b 68

(arrow) in Fig.6. Fig. 7,. mice on the 21st day.

5 Fig. 6,. Histological figure of rectum of experimental mice on the 14th day. Histological examination reveal crypt abscess (arrow) in Fig.6. Fig. 7,. Histological figure of rectum of experimental mice on the 21st day. Histological examination reveals ulcer formation (arrow) in Fig.7, and lymphocyte infiltration (arrow) in Fig.7. Fig. 8,. Histological figure of rectum of experimental mice on the 28th day. Aggregation of mast cells (arrow) is identified in a submucosal lower layer at Fig ) SEM Fig. 8a, b 60 1 cm Fig. 9a, b F i g. 10a, b 1 cm SEM Fig. 11a, b 69

in the mucosal layer of Fig. 10. Fig. 11.

6 Fig. 9,. Histological figure of rectum of experimental mice on the 60th day. Histological examination reveals mast cell infiltration (arrow) in submucosal layer, Fig. 9. Fig. 10,. Histological figure of rectum of experimental mice on the 90th day. Many macrophages (arrow) are identified in the mucosal layer of Fig. 10. Fig. 11. EM figure of rectum of normal mice by SEM ( 750) and SEM( 1500). Deep and narrow crypts (arrow) are seen in Fig. 11. Fig. 12. EM figure of rectum of experimental mice on the 3rd day (SEM( 750)) and (SEM( 1500)). Fig. 12, edematous change of villi and exposure of goblet cells (arrow) are seen in Fig

13, and aggregation of leukocytes (arrow) is seen

EM figures of rectum of experimental mice on the

Ulcer formation (arrow) is seen in Fig. 14 and.

A shallow large crypt (arrow) is seen in Fig. 15.

7 Fig. 13. EM figure of rectum of experimental mice on the 7th day (SEM( 750)) and (SEM ( 1500)). Disappearance of villous structure (arrow) in Fig. 13, and aggregation of leukocytes (arrow) is seen in Fig. 13. Fig. 14,. EM figures of rectum of experimental mice on the 14th day (SEM( 750)). Ulcer formation (arrow) is seen in Fig. 14 and. Fig. 15,. EM figures of rectum of experimental mice on the 21st day (SEM ( 750)). A shallow large crypt (arrow) is seen in Fig. 15. DSS 3 28 Fig.12a, b 7 Fig. 16a, b Fig.13a, b 14 Fig. 17a, b Fig. 14a, b Fig. 15a, b polypoid lesion 21 Fig. 18a, b 71

Fissure of colonic glands (arrow) is seen

EM figure of rectum of experimental mice

8 Fig. 16,. EM figures of rectum of experimental mice on the 28th day (SEM ( 750)). A shallow large crypt (arrow) is seen in Fig. 16. Fig. 17,. EM figures of rectum of experimental mice on the 60th day (SEM ( 750)). Fissure of colonic glands (arrow) is seen in Fig. 17. Fig. 18. EM figure of rectum of experimental mice on the 90th day (SEM ( 750)) and (SEM ( 1500)). A polypoid lesion (arrow) is seen in Fig. 18. M W 50, 000 MW 5,000 5 % 2 BALB/C % DSS UC % DSS S 1 % DSS UC 5 % D S S 72

9 DSS UC UC 6), 11)~27) DSS SEM UC DSS U C SEM 14), 15) DSS 17 ) 11 ) SEM UC 16), 18), 19) DSS UC 90 polypoid lesion DSS DSS 23 ) ~ 27 ) UC polypoid lesion 2 % DSS 2 1 % 2 % 3 UC Carrageenan 6)~10) DSS UC UC SEM 1) ; 36: 77. 2),,,,,.. Ulcer Research 1996; 23: ) ; 621: 6. 4),. Brown-Norway UC. Ther Res 2000; SEM 3 21: S ) Hibi T, Ogata H, Sakuraba A. Animal models of 7 inflammatory bowel disease. J Gastroenterology 2002; SEM 37:

10 6) Elson CO, Sartor RB, Tennyson GS, Riddell RH. 17),,,, Experimental models of inflammatory bowel disease.,. Dextran Sulfate. Ulcer Gastroenterology 1995; 109: Research 1998; 25: ),,,, 18),.,,,. Carrageenan. Ther Res 2001; 22: S ; 75: ),,,, 8) Onderdonk AB, Bartlett JG. Bacteriological studies of,,,,, experimental ulcerative colitis. Am J Clin Nutr 1979;.. 32: ; 22: ) Anver MR, Cohen BJ. Animal model of human 20). disease. Am J Pathol 1976; 84: ) Kitsukawa Y, Saito H, Suzuki Y, Kasanuki J, Tamura 1995; 43: Y, Yoshida S. Effect of ingestion of eicosapentaenoic 21),,,. acid ethyl ester on carrageenan-induced colitis in guinea pigs. Gastroenterology 1992; 102: Gastroenterological 11) Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Endosc 1988; 30: Clinicopathologic study of dextran sulfate sodium 22),,,, experimental murine colitis. Lab Invest 1993; 69: DSS NEM 12) Dieleman LA, Ridwan BU, Tennyson GS, Beagley. 1998; 95: KW, Bucy RP, Elson CO. Dextran sulfate sodiuminduced colitis in severe comnined immunodeficient,,. 23),,,, mice. Gastroenterology 1994; 107: ) Okayasu I, Hatakeyama S, Yamada M, Ohkusa T,. 1991; 3: 339- Inagaki Y, Nakaya R.A novel method in the induction 343. of reliable experimental acute and chronic ulcerative 24). colitis in mice. Gastroenterology 1990; 98: ) ; 90: ) ; 82: ),,,,. 1994; 46: ,,,,, 26). DSS, DMH,,,,.,,,,,,. 1995; 47: ,,. 27) Okayasu I, Yamada M, Mikami T, Yoshida T, Kanno J, Ohkusa T. Dysplasia and carcinoma development in Metronidazole. 1987; 84: experimental colitis. J Gastroenterol Hepatol 2002; 17: ),,,,,,,,,,,.. Gastroenterological Endosc 1992; 34:

11 Abstract A Morphological Study of the Gastrointestinal Mucosa in Experimental Ulcerative Colitis Toshifumi Takano, Takeshi Sakiyama, Chizuko Hashimito, Shigeko Ohnuma, Masayuki Takagi, Mamoru Tadokoro The developmental mechanism of ulcerative colitis (UC) is still unclear. Since progressive changes occurring in this condition have not been fully described in the literature, the authors carried out an experiment by giving a water solution of dextran sodium sulfate (DSS) to eight-week-old mice. A 2% water solution of DSS was given daily for 14 days (acute phase), and then a 1 % water solution of DSS was given daily for the following 90 days (chronic phase). Histological examinations of the colon revealed desquamation and regeneration of epithelium, crypt abscess, formation of ulcer as well as granulation and infiltration of lymphocytes, mast cells and macrophages. These findings are compatible with those in human ulcerative colitis. Scanning electron microscope revealed edematous changes and exposure of goblet cells on the third day, and then ulcer formations on the 14th day. In the chronic phase, regeneration of mucosa, ulcer formation, and fissure of the rectal gland were seen. Department of Pathology, St. Marianna University of Medicine, Japan. 75

熊本大学学術リポジトリ Kumamoto University Repositor Title 炎症性腸疾患に対する HSF1 及び HSP70 の保護的役割 Author(s) 田中, 健一郎 Citation Issue date Type URL Thesis or Di

熊本大学学術リポジトリ Kumamoto University Repositor Title 炎症性腸疾患に対する HSF1 及び HSP70 の保護的役割 Author(s) 田中, 健一郎 Citation Issue date 2008-03-25 Type URL Thesis or Dissertation http://hdl.handle.net/2298/9448 Right 1