Kudo Tetsuji, Matsumoto Takayuki, Nakamichi Ikuo, Yada Shinichiro, Esaki Motohiro, Jo Yukihiko, Ohji Yutaka, Yao Takashi, Iida Mitsuo
Department of Medicine, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan.
Scand J Gastroenterol. 2008;43(6):689-97. doi: 10.1080/00365520701864627.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis).
Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 microg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis.
Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01,<0.05,<0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001).
Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.
重组人粒细胞集落刺激因子（rhG-CSF）可能是治疗克罗恩病的有效方法。本研究旨在检测rhG-CSF对小鼠葡聚糖硫酸钠诱导的结肠炎（DSS结肠炎）的作用。
通过给小鼠饮用含3% DSS的水9天来诱导小鼠结肠炎。6至7周龄雌性BALB/c小鼠从第0天至第8天每天皮下注射rhG-CSF（100微克/千克）或磷酸盐缓冲盐水（PBS），并在第3、5、7和9天处死小鼠。获取横结肠、降结肠和直肠的组织标本，并用苏木精和伊红染色。对炎症的严重程度、范围、上皮损伤和隐窝丢失进行评分。进行TUNEL染色以评估上皮细胞凋亡。
与PBS治疗相比，rhG-CSF治疗显著减轻了体重减轻、粪便评分和结肠长度缩短（分别为p<0.01、<0.05、<0.01）。在第9天，rhG-CSF组直肠的炎症、上皮细胞损伤和隐窝丢失的组织学评分比PBS组轻（分别为p<0.01、0.05、0.01）。rhG-CSF组直肠中TUNEL阳性细胞的数量比PBS组少（p<0.001）。
rhG-CSF治疗通过抑制直肠黏膜炎症和上皮损伤改善小鼠DSS结肠炎。rhG-CSF的抗炎作用之前似乎先有预防上皮细胞凋亡的作用。
