Effects of hepatocyte growth factor on rat inflammatory bowel disease models

Effects of hepatocyte growth factor on rat inflammatory bowel disease models
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DOI:
10.1007/s10620-005-2664-z
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发表时间:
2005-05-01
影响因子:
3.1
通讯作者:
Matsumoto, T
Matsumoto, T
中科院分区:
医学3区
文献类型:
--
作者:
Ohda, Y;Hori, K;Matsumoto, T

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肝细胞生长因子(HGF)是一种肝营养因子,并且还具有上皮生长因子的功能。我们检测了 HGF 对三硝基苯磺酸或葡聚糖硫酸钠诱导的大鼠炎症性肠病模型的治疗作用。使用腹膜内植入泵以50μg/体/天连续施用重组人HGF 7天。 HGF治疗减少了两种模型的溃疡面积、组织学损伤评分、粘膜髓过氧化物酶活性和上皮细胞凋亡率,但没有增加上皮细胞有丝分裂率以及作为上皮细胞增殖指标的增殖细胞核抗原、Ki-67和溴脱氧尿苷的免疫组织化学标记指标。然后,我们检查了 HGF 受体 c-met 的上皮定位,并在表面上皮上发现了它,观察到细胞凋亡,但在增殖区没有发现它。这些结果表明,在这些炎症性肠病模型中,HGF 通过抗炎症(包括抗细胞凋亡)而不是上皮细胞增殖来发挥治疗作用。
Hepatocyte growth factor (HGF) is a hepatotrophic factor and, also, functions as an epithelial growth factor. We examined the therapeutic effects of HGF on rat inflammatory bowel disease models induced by trinitrobenzensulfonic acid or dextran sulfate sodium. Recombinant human HGF was continuously administered at 50 mu g/body/day using an intraperitoneally implanted pump for 7 days. Treatment of HGF reduced the ulcerated area, histological damage score, mucosal myeloperoxidase activity, and epithelial apoptotic rate but did not increase epithelial mitotic rate and immunohistochemical labeling indexes of proliferating cell nuclear antigen, Ki-67, and bromodeoxyuridine as indexes of epithelial cell proliferation in either model. We then examined the epithelial localization of the HGF receptor c-met and identified it on the surface epithelia, where apoptosis was observed, but did not find it in the proliferative zone. These results suggest that HGF exhibits therapeutic effects via anti-inflammation including antiapoptosis rather than epithelial cell proliferation in these inflammatory bowel disease models.