阿尔茨海默病模型小鼠脑多巴胺D_2受体的研究

EXPLORATION OF CENTRAL DOPAMINE D_2 RECEPTOR IN ALZHEIMER DISEASE MODEL RATS

1目的 探讨阿尔茨海默病 (AD)小鼠模型多巴胺 D2 受体的变化及其与记忆等变化之间的关系。 2方法 采用毒蕈碱 (M)受体阻断剂东莨菪碱 (Sco)建立与 AD记忆障碍相似的小鼠模型 ,分别给予模型及对照组小鼠尾静脉注射 1 2 5 I- IBZM,2 h后断头、取脑 ,行冠状面冷冻切片放射自显影及图像分析。 3结果 模型 10 d( )组及40 d ( )组遭电击次数分别为 (0 .86± 0 .12 ) m in- 1 ,(0 .92± 0 .16 ) min- 1 ,而对照组分别为 (0 .2 6± 0 .0 4) min- 1 和(0 .2 2± 0 .0 6 ) min- 1 ,与对照组比较差异有显著性 (t=13.5 4,11.91,P<0 .0 5 ) ;模型组间比较差异有显著性 (t=2 .89,P<0 .0 5 )。 D2 受体放射自显影图像分析示 , 组脑纹状体 (ST) /额叶 (FC)放射性摄取比值分别为 4.173±0 .2 81,3.897± 0 .2 74,均明显低于对照组 (t=5 .87,7.16 ,P<0 .0 5 ) ; , 组间比较差异显著 (t=3.2 1,P<0 .0 5 )。4结论 多巴胺 D2 受体示踪剂 1 2 5 I- IBZM能够敏感地反映出 AD模型鼠 ST D2 受体的下降 ,D2 受体显像将为阐明AD的发病机制提供重要的分子核医学手段。

Objective To investigate the change of dopamine D 2 receptor and its relationship with memory in Alzheimer disease (AD) model rate using D 2 imaging agent 125 I IBZM.\ Methods\ AD model rats which memory loss similar to the amnesia of AD patients were established by giving muscarinic receptor antagonist scopolamine(Sco). 125 I IBZM was injected into the model and control rats through the tail vein, 2h after injection the brains were rapidly removed, sectioned coronally with a microtome, exposed and developed into autoradiogram and analyzed in GS 250 image analysis system.\ Results\ After they were given Sco, the rats recent memory degenerated, the number of 10d (group Ⅰ) and 40d (group Ⅱ) model rats hit by electrical stimulus were (0.86±0.12)min -1 and (0.92±0.16)min -1 respectively. It was significantly more than that of the control rats (0.26±0.04)min -1 and (0.22±0.06)min -1 ( t=13.54,11.91,P <0.05), and there also showed significant difference between Ⅰ and Ⅱ model group ( t=2.89,P <0.05). The 125 I IBZM D 2 autoradiography and analysis showed that the striatum (ST)/frontal cortex(FC) uptake ratio was 4.173±0.281, 2.897±0.27 for Ⅰ and Ⅱ model rats, respectively, it was lower than that of the control rats ( t=5.87,7.16,P <0.05), and it was significant difference between Ⅰ and Ⅱ model group ( t=3.21,P <0.05).\ Conclusion\ D 2 imaging agent 125 I IBZM could sensitively reflect the reduction of D 2 receptor in ST in AD model which consistent with the memory loss. We suppose that the D 2 imaging might afford an important molecular nuclear medical measure to clarify the mchanism of AD. [