The DPP-IV inhibitor ER-319711 has a proliferative effect on the colonic epithelium and a minimal effect in the amelioration of colitis
The DPP-IV inhibitor ER-319711 has a proliferative effect on the colonic epithelium and a minimal effect in the amelioration of colitis
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DOI：
10.3892/or.2011.1223
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发表时间：
2011-06-01
期刊：
影响因子：
4.2
通讯作者：
Fujiyama, Yoshihide
中科院分区：
文献类型：
--
作者：
Ban, Hiromusu;Bamba, Shigeki;Fujiyama, Yoshihide
二肽基肽酶IV（DPP-IV）抑制剂预期可延长胰高血糖素样肽（GLP-2）和GLP-1的半衰期，并可促进上皮细胞增殖和再生。本研究的目的是调查是否DPP-IV抑制剂可以促进上皮细胞增殖和减弱葡聚糖硫酸钠（DSS）诱导的结肠炎。对9周龄雌性C57/B6小鼠单次给予ER-319711，以评估血浆GLP-2浓度的变化。将10只小鼠分成两组：媒介物组和ER-319711组。ER-319711经口给药7天。然后在第7天处死前2小时，腹膜内给予小鼠溴脱氧尿苷（BrdU）。将26只小鼠分成三组：媒介物组、DSS诱导的结肠炎组和用ER-319711处理的DSS诱导的结肠炎组。给予小鼠DSS 5天，并在第14天处死。血浆GLP-2水平在对ER-319711的反应中升高。ER-319711组从第1天至第3天体重显著降低。ER-319711组中每个隐窝的BrdU阳性细胞数和隐窝高度增加。DSS + ER-319711组的体重转变降低。疾病活动指数和结肠长度显示DSS + ER-319711组结肠炎改善。DPP-IV抑制剂被认为促进肠上皮细胞的增殖。然而，DSS诱导的结肠炎的改善仅是部分的。
Dipeptidyl-peptidase IV (DPP-IV) inhibitors are expected to prolong the half-life of Glucagon-like peptide (GLP-2) as well as GLP-1, and may result in the promotion of epithelial cell proliferation and regeneration. The aim of this study was to investigate whether a DPP-IV inhibitor can promote epithelial proliferation and attenuate dextran sodium sulfate (DSS)-induced colitis. Nine-week-old female C57/B6 mice were given a single dose of ER-319711 to assess the changes in plasma GLP-2 concentrations. Ten mice were divided into two groups: a vehicle group and an ER-319711 group. ER-319711 was administered orally for 7 days. The mice were then given bromodeoxyuridine (BrdU) intraperitoneally 2 h before sacrifice on day 7. Twenty-six mice were divided into three groups: a vehicle group, a DSS-induced colitis group and a DSS-induced colitis treated with ER-319711 group. The mice were given DSS for 5 days and sacrificed on day 14. Plasma GLP-2 levels were elevated in response to ER-319711. The ER-319711 group had a significantly decreased body weight from days 1 to 3. The number of BrdU positive cells per crypt and the crypt height were increased in the ER-319711 group. The DSS + ER-319711 group had a decreased body weight transition. The disease activity index and colon length showed an amelioration of colitis in the DSS + ER-319711 group. DPP-IV inhibitors are thought to promote the proliferation of the intestinal epithelium. However, the amelioration of DSS-induced colitis was only partial.