鱼藤酮处理大鼠脑内VMAT2及TPH、5-HT的表达改变  

Altered expression of VMAT2, TPH and 5-HT in rotenone-treated rats

作　　者：刘扬[1] 纪晓明[2] 李颖坤 康云霄[2] 张庆祝[2] 李双成[2] LIU Yang;JI Xiao-ming;LI Ying-kun;KANG Yun-xiao;ZHANG Qing-zhu;LI Shuang-cheng(Department of Neurobiology, the Hebei Medical University,Shijiazhuang 050017, China)

机构地区：[1]首都医科大学燕京医学院解剖教研室,北京101300 [2]河北医科大学神经生物学研究室

出　　处：《脑与神经疾病杂志》2016年第10期607-612,共6页Journal of Brain and Nervous Diseases

基　　金：河北省自然科学基金(C2009001094);河北省科技计划项目(12277728);首都医科大学燕京医学院科研启动基金(2013)

摘　　要：目的观察鱼藤酮处理大鼠脑内单胺囊泡转运体2(VMAT2)。色氨酸羟化酶(TPH)及5—羟色胺(5—HT)的表达变化;探讨其对5—HT能神经元的影响及可能机制。方法选用健康、成年雄性Wistar大鼠,背部皮下注射鱼藤酮3d或28d制作大鼠动物模型;利用免疫细胞化学分析VMAT2在大鼠黑质、中缝背核和尾壳核以及TPH、5—HT在中缝背核的表达变化;以透射电镜观察轴突超微结构的改变,探讨鱼藤酮毒性作用的可能机制。结果鱼藤酮3d组:(1)鱼藤酮组大鼠黑质、中缝背核VMAT2的表达增加,免疫反应强度吸光度值显著高于对照组;尾壳核VMAT2的表达减弱,免疫反应强度吸光度值明显低于对照组(P<0.01);(2)鱼藤酮组大鼠中缝背核TPH、5—HT的表达减少,免疫反应强度吸光度值显著低于对照组(P<0.01);(3)透射电镜观察显示鱼藤酮处理大鼠中缝背核轴突变性、其内微管解聚。鱼藤酮28d组:(1)鱼藤酮组大鼠黑质、中缝背核及尾壳核VMAT2的表达均减弱,免疫反应强度吸光度值显著低于对照组(P<0.01或P<0.05);(2)与对照组相比,鱼藤酮组大鼠中缝背核TPH、5—HT的表达降低,免疫反应强度吸光度值显著低于对照组(P<0.01)。结论鱼藤酮降低5—HT能神经元TPH、5—HT的表达,其毒性作用可能与轴突微管解聚导致突触囊泡VMAT2轴浆顺行转运障碍有关。Objective To study the altered expression of vesicular monoamine transporter2(VMAT2),tryptophan hydroxylase( TPH) and serotonin( 5-HT) in rotenone-treated rats and investigate the possible mechanismof rotenone toxicity to serotonergic neurons. Method Rotenone was injected subcutaneously to the back of Wistar ratsto establish a rotenone-treated rat model. Immunocytochemistry was mainly used to analyze the altered expression ofVMAT2, TPH and 5-HT in the brain of rats. Transmission electron microscope( TEM) was used to analyze the axonalultrastructures. Results Rotenone-treated 3-day group: ① Immunocytochemistry showed the expression of VMAT2was much stronger in substantia nigra( SN) and dorsal raphe nucleus( DRN) in rotenone-treated rats than that incontrol, however, the expression of VMAT2 in caudate-putamen( CPu) was much lower in rotenone-treated rats thanthat in control(P<0.01). ② Immunocytochemistry showed the expression of both TPH and 5-HT were significantlylower in DRN of rotenone-treated rats than that in control( P<0.01). ③ TEM showed the depolymerized microtubulesin axons of DRN in 3-day rotenone-treated rats. Rotenone-treated 28-day group: ① Immunocytochemistry showed theexpression of VMAT2 was significantly lower in SN, DRN and CPu of rotenone-treated rats than that in control( P<0.01or P<0.05). ② Immunocytochemistry showed the expression of both TPH and 5-HT were significantly lower in DRNof rotenone-treated rats than that in control( P<0.01). Conclusion Rotenone decreased the expression of TPH and5-HT of serotonergic neurons and its toxicity was related to the dysfunction of axoplasmic transport synaptic vesiclesdue to depolymerized microtubules.

关 键 词：单胺囊泡转运体2 5—羟色胺 色氨酸羟化酶 鱼藤酮 大鼠 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]