两点单侧注射前脑内侧束建立PD大鼠模型及其行为学评价

目的6-羟基多巴胺(6-OHDA)两点单侧注射前脑内侧束建立帕金森病(PD)大鼠模型,从行为学角度对模型进行评价。方法104只SD大鼠随机分为正常对照组(n=14),生理盐水对照组(n=35)和模型组(n=55)。模型组SD大鼠以6-OHDA立体定向两点单侧注射至前脑内侧束。术后不同时间点(第7、14、21、28天)进行行为学分析(姿势不对称性、前肢始动不能试验);术后第1周开始,每周1次腹腔注射阿朴吗啡(Apo)诱发大鼠旋转行为,连续6周,分别计数阳性大鼠例数。结果模型组大鼠姿势不对称性和前肢始动不能试验指标与正常对照组和生理盐水对照组比较,有显著差异(P<0.01);其行为学不对称性随时间延长而逐渐加重,至28 d后趋于稳定。第1、2、3、4周Apo诱发模型组大鼠旋转行为的阳性例数分别为9、12、12、1。结论前脑内侧束单侧注射6-OHDA诱发大鼠的行为学改变与PD患者临床表现有相似之处。Apo诱发的PD模型大鼠旋转行为次数随损毁时间延长而增加,与其行为不对称性随时间延长加重的表现一致。实验为深入研究帕金森病发病机制奠定了基础。

Establishment of Parkinson disease rat model by two-spot unilaterally injection into medial forebrain bundle and its ethology assessment

Objective To establish the Parkinson disease(PD) rat model by two-spot unilaterally injecting 6-hydroxydopamine(6-OHDA) into the medial forebrain bundle and evaluate this model in ethology. Methods One hundred and four SD rats were randomly divided into three groups: normal control group(n=14),physiological saline control group(n=35) and model group(n=55).The model group was two-spot unilaterally injected with 6-OHDA into the medial forebrain bundle.Ethology analysis(posture asymmetry,anterior limb akinesia) was conducted at different time(the 7th,14 th,21st and 28th day).From the beginning of the first week after operation,apomorphine(Apo) was intraperitoneally injected once a week to induce the rotational behavior,for a consecutive of 6 weeks.The number of well-established lesion rats was counted. Results There was significant differences in the parameters of posture asymmetry and anterior limb akinesia between the model group and saline control and normal control groups(P<0.01).The severity of ethological asymmetry increased with time and trended steady 28 days later.The number of positive model after Apo injection at the 1st,2nd,3rd and 4th week was 9,12,12 and 1,respectively. Conclusion The ethological change of rats induced by unilaterally injection of 6-OHDA into the medial forebrain bundle resembles the symptoms of PD patients.The rat's rotation behavior induced by Apo increases with time,and the tendency is in accordance with the change of asymmetry behavior. This experiment lays a foundation for the intensive research on pathogenesis of PD.