Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, PO Box 17666, United Arab Emirates.
World J Gastroenterol. 2011 Sep 7;17(33):3836-41. doi: 10.3748/wjg.v17.i33.3836.
To examine the influence of ghrelin on the regenerative potential of gastrointestinal (GI) epithelium.
Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin (10 and 6 mg/kg). Some of the doxorubicin-treated mice received a continuous subcutaneous infusion of ghrelin (1.25 μg/h) for 10 d via implanted mini-osmotic pumps. To label dividing stem cells in the S-phase of the cell cycle, all mice received a single intraperitoneal injection of 5'-bromo-2'-deoxyuridine (BrdU) one hour before sacrifice. The stomach along with the duodenum were then removed and processed for histological examination and immunohistochemistry using anti-BrdU antibody.
The results showed dramatic damage to the GI epithelium 3 d after administration of chemotherapy which began to recover by day 10. In ghrelin-treated mice, attenuation of GI mucosal damage was evident in the tissues examined post-chemotherapy. Immunohistochemical analysis showed an increase in the number of BrdU-labeled cells and an alteration in their distribution along the epithelial lining in response to damage by doxorubicin. In mice treated with both doxorubicin and ghrelin, the number of BrdU-labeled cells was reduced when compared with mice treated with doxorubicin alone.
The present study suggests that ghrelin enhances the regenerative potential of the GI epithelium in doxorubicin-treated mice, at least in part, by modulating cell proliferation.
研究 ghrelin 对胃肠道（GI）上皮再生潜能的影响。
通过两次静脉注射阿霉素（10 和 6mg/kg）诱导小鼠 GI 上皮损伤。一些阿霉素处理的小鼠通过植入的迷你渗透泵接受持续 10 天的 ghrelin（1.25μg/h）皮下输注。为了标记细胞周期 S 期的分裂干细胞，所有小鼠在处死前 1 小时接受单次腹腔注射 5'-溴-2'-脱氧尿苷（BrdU）。然后取出胃和十二指肠进行组织学检查和抗 BrdU 抗体免疫组织化学染色。
结果显示，化疗后 3 天 GI 上皮出现明显损伤，第 10 天开始恢复。在 ghrelin 处理的小鼠中，化疗后组织中明显减轻了 GI 黏膜损伤。免疫组织化学分析显示，BrdU 标记细胞的数量增加，并且其在受到阿霉素损伤时沿着上皮衬里的分布发生改变。与单独用阿霉素处理的小鼠相比，同时用阿霉素和 ghrelin 处理的小鼠中 BrdU 标记细胞的数量减少。
本研究表明，ghrelin 通过调节细胞增殖至少部分增强了阿霉素处理的小鼠的 GI 上皮的再生潜能。
