脑源性神经营养因子对大鼠内脏痛的作用

Modulation effect of brain-derived neurotrophic factor on visceral pain in rat

目的：探讨脑源性神经营养因子（BDNF）对雌、雄大鼠内脏痛的作用.方法：雌、雄大鼠以腹腔注射乙酸建立内脏痛模型.在注射乙酸之前60min,大鼠腹腔注射anti-BDNF抗体,然后观察注射乙酸后60min内的行为学变化,计算扭体次数;行为学观察完成后,大鼠立即处死,用免疫组织化学方法观察即早基因c-Fos编码产物c-Fos蛋白在前扣带皮质（ACC）的表达.结果：雌、雄大鼠腹腔注射乙酸后出现明显的内脏痛反应,扭体次数增加.对于雌性大鼠,腹腔注射乙酸之前给予anti-BDNF抗体可降低扭体次数;而对于雄性大鼠,可增加扭体次数.免疫组织化学显色显示,雌、雄大鼠腹腔注射乙酸后ACC内出现大量c-Fos免疫阳性产物;对于雌性大鼠,腹腔注射乙酸之前给予anti-BDNF抗体可降低ACC内c-Fos免疫阳性产物的数量;而对于雄性大鼠,可增加ACC内c-Fos免疫阳性产物的数量.结论：BDNF参与大鼠内脏痛的调节,并具有性别差异.对于雌性大鼠BDNF可能促进内脏痛反应,而对于雄性大鼠BDNF可能具有相反的作用.

Objective： To investigate the involvement of brain-derived neurotrophic factor （BDNF） in the model of visceral hypersensitivity for both male and female rats. Methods： The model of visceral hypersensitivity was established by intraperitoneal injection of acetic acid. For the experimental groups, an additional injection of anti-BDNF antibody was given 1 hour before acetic acid injection. The intensity of noxious visceral stimulus, assessed by the number of abdominal contraction, were recorded during the 1 hour after injection of acetic acid. The rats were sacrificed by the end of behaviour index evaluation. The expression pattern of c-Fos in the anterior cingulate cortex （ACC） was determined by immunohistochemistry. Results： An obvious abnormal behaviour was witnessed after the injection of acetic acid with a great increase in the number of abdominal contraction. However, for the experimental group rats, the ones that received anti-BDNF antibody before acetic acid injection, the behaviour index showed an increase in male but a decrease in female. The result of immunohistochemistry revealed that after the injection of acetic acid, the expression of c-Fos in the ACC was up-regulated. And, for the experimental group it demonstrated an enhancement in male but a weakening in female. Conclusion： BDNF plays a critical role in the modulation of visceral hypersensitivity, which is sex-depended. BDNF might contribute to the visceral hypersensitivity in female while perform an opposite effect in male.