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目的探讨托吡酯(TPM)对戊四氮(PTZ)致癫幼鼠血清促胃液素(GAS)及下丘脑增食欲素A(orexinA)及其与体质量变化的关系。方法28日龄健康Wistar大鼠120只随机分为4组:空白组、TPM对照组、PTZ模型组、TPM治疗组,每3d测1次体质量,分别在实验2、4、6周末应用放射免疫法测定其血清GAS水平,免疫组织化学法测定其下丘脑orexinA表达。结果TPM对照组、TPM治疗组在第3周末较其他2组体质量明显降低,4周末降至最低点;4周末时,TPM对照组与空白组比较、TPM治疗组与PTZ模型组比较,血清GAS水平均显著降低(Pa<0.05)。PTZ模型组较空白组、TPM治疗组较TPM对照组血清GAS水平显著下降(Pa<0.05);TPM治疗组与空白组及PTZ模型组比较,下丘脑orexin A阳性神经元细胞数均显著降低(Pa<0.05)。6周末时,TPM治疗组与空白组、TPM对照组比较,PTZ模型组与空白组比较,血清GAS水平均显著降低(Pa<0.05);TPM对照组与空白组比较,TPM治疗组与PTZ模型组比较,血清GAS水平无显著变化;TPM对照组、TPM治疗组与空白组及PTZ模型组比较,下丘脑orexin A阳性神经元细胞数降低,但无统计学差异;PTZ模型组与空白组、TPM治疗组与TPM对照组比较,下丘脑orexin A阳性神经元细胞数降低,但无显著差异。结论TPM可使大鼠体质量减轻,GAS可能参与大鼠体质量的调节过程,但不是引起体质量下降的直接原因。而orexin A表达减少有可能是TPM引起体质量减轻原因之一。
Objective To investigate the relationship between topiramate (TPM) and serum gastrin (GAS) and orexin A (Hypothalamic orexin A) induced by PTZ in epileptic rats. Methods Twelve healthy 28-day-old Wistar rats were randomly divided into 4 groups: blank group, TPM control group, PTZ model group and TPM treatment group. Body mass was measured every 3 days. Serum GAS levels were measured by immunohistochemistry and orexinA expression in hypothalamus was measured by immunohistochemistry. Results Compared with the other two groups, the body weight of the TPM control group and the TPM treatment group decreased significantly at the end of the third week and dropped to the lowest level at the end of the fourth week. Compared with the TPM control group and the PTZ treatment group, GAS levels were significantly lower (Pa <0.05). The levels of serum GAS in TPM-treated group were significantly lower than those in TPM-treated group (P <0.05), and the number of orexin A positive neurons in hypothalamus was significantly decreased in PTM-treated group compared with blank group and PTZ model group Pa <0.05). At the end of 6th week, compared with the blank group and the TPM control group, the levels of serum GAS in the PTZ model group were significantly decreased (P <0.05); TPM control group and the PTZ model group The level of serum GAS had no significant change in TPM control group and TPM treatment group compared with blank group and PTZ model group, the number of orexin A positive neurons in hypothalamus decreased, but there was no statistical difference; PTZ model group and blank group, TPM treatment group and TPM control group, the hypothalamus orexin A positive neurons decreased, but no significant difference. Conclusion TPM can reduce the body weight of rats, GAS may be involved in the regulation of body weight in rats, but not the direct cause of weight loss. However, the decrease of orexin A expression may be one of the reasons for the weight loss caused by TPM.