6-羟基多巴胺损毁单侧内侧前脑束与单侧纹状体大鼠模型的病变早期比较  

Comparison of unilateral medial forebrain bundle and unilateral striatum lesioned by 6-hydroxydopamine at early lesioned stage in rat model

作　　者：孙炜 吴春明[1] 刘张[2] 难波宏树 Sun Wei;Wu Chunming;Liu Zhang;Namba Hiroki(Dept of Neurosurgery,The First Affiliated Hospital of Dalian Medical University,Dalian 116011;Dept of Pediatrics,The First Affiliated Hospital of Dalian Medical University,Dalian 116011;Dept of Neurosurgery,Hamamatsu University School of Medicine,Hamamatsu,Japan 431-3192)

机构地区：[1]大连医科大学附属第一医院神经外科,大连116011 [2]大连医科大学附属第一医院儿科,大连116011 [3]日本滨松医科大学附属医院神经外科,滨松431-3192

出　　处：《安徽医科大学学报》2023年第4期554-560,共7页Acta Universitatis Medicinalis Anhui

基　　金：辽宁省自然科学基金(编号:2019-ZD-0639);大连市科技创新基金(编号:2019J13SN104)。

摘　　要：目的 比较6-羟基多巴胺(6-OHDA)损毁的单侧内侧前脑束(MFB)与单侧纹状体大鼠模型成模4周后多巴胺(DA)系统中神经递质功能变化。方法 选择62只成年雄性Sprague-Dawley大鼠,随机分为4组:1位点模型组(n=18,1个位点纹状体损毁)、4位点模型组(n=18,4个位点纹状体损毁)、MFB模型组(n=18,MFB损毁)和假手术对照组(n=8)。运用免疫组织化学酪氨酸羟化酶(TH)染色方法统计阳性DA神经元脱失率,运用体外放射配体-受体结合实验、行为学实验和小动物正电子发射断层扫描(PET)检测四组模型DA转运蛋白(DAT)和D2受体的放射活性结合率的变化。结果 TH免疫组化染色结果显示,1、4位点模型组和MFB模型组病灶侧TH阳性细胞脱失率分别为19.1%、 84.7%、97.1%,提示模型制作成功。DAT和D2受体检测结果显示:与假手术对照组相比,1、4位点模型组及MFB模型组病侧DAT放射活性结合率均下降(P<0.05、P<0.05和P<0.01),且4位点模型组的下降程度明显高于1位点模型组(P<0.05),MFB模型组的下降程度明显高于1、4位点模型组(P<0.01);与假手术对照组相比,1、4位点模型组病侧D2受体放射活性结合率均下降(P<0.05),MFB模型组病侧D2受体放射活性结合率升高(P<0.05)而1、4位点模型组间的下降程度比较无统计学差异。DAT和D2受体在假手术对照组大鼠病侧与健侧的分布无差异。甲基苯丙胺可诱导3个模型组产生朝向病灶同侧的旋转,但3个模型组之间的旋转差异无统计学意义;溴隐亭可诱发1、4位点模型组产生朝向病灶同侧的旋转,但引发MFB模型组朝向病灶对侧的旋转,1、4位点模型组之间的旋转差异无统计学意义;步行实验结果显示,3个模型组病侧肢体运动启动时间明显长于健侧、步长长度明显短于健侧、步伐调整数明显少于健侧(P<0.001),但3个模型组间病侧的启动时间、步长长度和步伐调整数比较后差异无统计学意义。结论 纹状体和MObjective To compare the functional changes of neurotransmitters in the dopamine(DA)system of rats lesioned by 6-hydroxydopamine in unilateral medial forebrain bundle(MFB)and unilateral striatum after 4 weeks of modeling.Methods Adult male Sprague-Dawley rats(n=62)were divided randomly into four groups:single-site model(one site striatal lesion model,n=18),four-site model(four sites striatal lesion model,n=18),MFB model(MFB lesion model,n=18)and a sham operated control group(n=8).Immunohistochemical tyrosine hydroxylase(TH)staining was used to calculate the loss rate of positive DA neurons.The functional changes of dopamine transporters(DAT)and D2 receptors in rat models of four groups were detected by radioligand-receptor binding assay in vitro,behavioral test and small-animal PET.Results Immunohistochemical staining results of TH at 1-lesion,4-lesion and MFB model showed that the TH-positive cell loss rates of the lesion side in three models were 19.1%,84.7%and 97.1%,respectively,indicating that the model was successfully constructed.The results of DAT/D2 receptor functions in the three models showed that,compared with the sham operated control group,the DAT binding ratio of radioactivity on the lesion side of 1-lesion,4-lesion and MFB model significantly decreased(P<0.05,P<0.05 and P<0.01).The DAT binding ratio of radioactivity on the lesion side was compared among 1,4 lesion and MFB model.It was found that the decrease degree of MFB model was significantly higher than that of the previous two models(P<0.01),and the decrease degree of 4-lesion model was significantly higher than that of 1-lesion model(P<0.05).Compared with the sham operated control group,the D2 receptor binding ratio of radioactivity on the lesion side of 1-lesion and 4-lesion model significantly decreased(P<0.05),and there was no significant difference in the degree of decrease between the two models,but the D2 receptor binding ratio of radioactivity on the lesion side of MFB model significantly increased(P<0.05).There was no difference in th

关 键 词：帕金森病 多巴胺转运蛋白 多巴胺D2受体 6-羟基多巴胺 正电子发射断层扫描 大鼠模型 

分 类 号：R363.1[医药卫生—病理学]