托吡酯对戊四氮致幼鼠体质量及血清促胃液素和下丘脑增食欲素的影响

Effects of Topamax on Changes of Weight and Levels of Serum Gastrin and Expression of Orexin in Hypothalamus of Pentetruzole Induced Epileptic Rats

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 explore the effects of topiramate（TPM）on levels of serum gastrin（GAS）,the expression of orexin A in hypothalamus,and their relationship with weight changes in pentetruzole-induced epileptic rats.Methods One hundred and twenty Wistar rats（28 days）were divided into 4 groups randomly：blank group,TPM control group,Pentylenetertrazole（PTZ）model group,and TPM therapy group.Weight changes were measured every 3 days.The level of serum GAS and the expressing of orexin A in hypothalamus were detected by radioimmunity and immunohistochemicaliy method respectively on the 2nd,4th,6th weekends.Results TPM control group and TPM therapy group showed a decrease in rat weight,compared with the other 2 groups on the 3rd weekend,and fell to the nadir on the 4th weekend;by the 4th weekend：the levels of serum GAS descended markedly,in comparison of the TPM therapy control group with the blank group,and the TPM therapy group with the PTZ model group（Pa0.05）;it was the same in comparison of PTZ model group with the blank group and the TPM therapy group with the TPM control group（Pa0.05）;and orexin A in hypothalamus descended significantly in comparison of the TPM group with the blank group,the PTZ model group（Pa0.05）.By the 6th weekend：the levels of serum GAS descended markedly in comparison of the TPM treated group with the blank group and TPM control group,and PTZ model group with the blank group（Pa0.05）;the level of serum GAS did not show significant change,in comparison of TPM control group with blank group,TPM therapy group with PTZ model group.Orexin A in hypothalamus did not show significant change in comparison of TPM control group,TPM therapy group with the blank group,PTZ model group;it was the same in comparison of the PTZ model group with blank group and TPM therapy group with TPM control group.Conclusions TPM may reduce the rat＇ weight,which has something to do with descending the expression of orexin A in hypothalamus,but it has no direct association with descending the level of serum GAS.