Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1.1. Seiryo-machi, Aobaku, Sendai 980-8574, Japan.
Gut. 2013 Jan;62(1):6-14. doi: 10.1136/gutjnl-2011-301389. Epub 2012 Jan 27.
There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage.
An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17β-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery.
While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17β-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17β-oestradiol.
This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.
食管腺癌存在强烈的男性优势,这可能与男性比女性更普遍存在侵蚀性反流性食管炎等前期病变有关。本实验研究了大鼠反流性食管炎模型中的性别差异,并探讨了雌激素在控制食管组织损伤中的潜在作用。
通过手术在雄性和雌性大鼠中产生酸反流性食管炎模型,并在饮食中添加抗坏血酸,在饮水中添加亚硝酸钠,以刺激腔内外源性一氧化氮(NO)作为加重剂。手术后 7 天,切除食管,测量损伤面积、髓过氧化物酶活性和促炎细胞因子水平。此外,给去卵巢雌性大鼠或雄性大鼠给予 17β-雌二醇,然后进行反流性食管炎手术。
在基础模型中,食管损伤在性别之间没有差异,但在外源性 NO 给药时,男性的食管损伤比女性更严重。与假去卵巢组相比,去卵巢大鼠的食管损伤增加,但 17β-雌二醇的替代可减轻加重的食管损伤。此外,17β-雌二醇抑制了雄性大鼠加重的食管损伤。
这是第一项研究表明,在与胃食管反流病相关的动物模型中,食管组织损伤的严重程度存在明显的性别差异,强调了雌激素在控制胃食管反流病相关的食管上皮损伤中的关键作用。