6-羟基多巴胺制备帕金森病大鼠模型的神经行为学特点

Characteristics of neuroethology in rat models with Parkinson disease induced by 6-hydroxy dopamine

目的:采用在大鼠脑右侧黑质注射6-羟基多巴胺制备帕金森病模型,观察帕金森病模型大鼠神经行为学的特点。方法:实验于2001-03/12在上海中医药大学病理学实验室完成。将62只Wistar大鼠随机分为3组。模型组:采用6-羟基多巴胺(溶于含0.2g/L抗坏血酸的生理盐水中,浓度为2g/L,以1.0mm/min速度缓慢进针,3μL/孔,注射速度为1μL/min,注射完毕后留针5min,然后以1.0mm/min速度缓慢退针)。注射于大鼠脑右侧黑质造成偏侧帕金森病模型。假手术组:注射含0.2g/L抗坏血酸的等量生理盐水,其余条件与模型组相同。正常对照组:不进行任何处理。在模型制备后第10天,以腹腔注射阿朴吗啡0.5mg/kg诱发大鼠向一侧旋转,记录开始旋转至30min内的旋转圈数,以旋转圈数平均每分钟超过7次者为合格的帕金森病模型。并观察各组大鼠在第45天的旋转行为。结果:62只大鼠中有23只大鼠造模不成功,39只大鼠进入结果分析。①正常对照组、假手术组无旋转行为。模型组在腹腔注射阿朴吗啡后0.5～4min,均开始出现旋转行为,即以左侧后肢为支点原地旋转,头尾相接,身体成环状,同时还伴有觅食、嗅探动作。②42只模型组大鼠中,造模成功19只,成功率为45%(19/42)。向左旋转的大鼠显著多于向右旋转及向左一圈,右一圈旋转的大鼠[14只,4只,1只,(P<0.05)]。③模型组在第45天的旋转圈数与第10天时接近[(526.10±173.96),(538.52±187.88)圈/h,(t=1.448,P>0.05)]。结论:①模型大鼠具有典型的神经行为学特点,主要表现为以健侧后肢为支点原地旋转。②该模型不能自行恢复,是研究帕金森病的稳定、可靠模型。

AIM： With the injection of 6-hydroxy dopamine on the black substance of right-sidedness brain in rats to make Parkinson disease （PD） models, to observe the characteristics of neuroethology in model rats with PD, METHODS： The experiment was completed in the Laboratory of Pathology of Shanghai University of Traditional Chinese Medicine between March and December 2001, Sixty-two Wistar rats were assigned randomly into 3 groups, Model group： The partial side PD model led by black substance of right-sidedness brain in rats was injected with 6-hydroxy dopamine （dissolving in the saline with 0.2 g/L ascorbic acid, 2 g/L concentration, slowing entering needle at the speed of 1,0 mm per minute, 3μL per hole, at the speed of 1μL per minute injection, after injection detaining for 5 minutes, and then slowly made the needle back at the speed of 1,0 mm per minute）. Sham operation group： The equivalence saline containing 0,2 g/L ascorbic acid was injected, and the other conditions were the same to model group, Normal control group： Without doing any disposal, At the 10^th day after the models was made. The 0,5 mg/kg apomorphine was injected into abdominal cavity to induce the rats＇rotation towards one side to record the rotary circles from the beginning of rotation to 30 minutes, The PD models whose circles were at the average of over 7 times per minute were eligibility. And the behavior of rotation in rats in every group was observed at the 45^th day. RESULTS： Twenty-three rat models were failure among the 62 rats, and 39 rats were involved in the result analysis.①No rotary behavior appeared in the normal control group and sham operation group, All the rats in model group started to rotate 0.5-4 minutes after being injected apomorphine into the abdominal cavity, i,e,, the rats did original-place rotation by using its left-side posterior limb as the fulcrum, connecting head and tail and forming the whole body cyclic, meanwhile action of looking for foods and smelling were appeared, ② Among the 42 rats, 19 got successful modeling with the success rate of 45% （19/42）. The rats that rotated towards left were significantly more than that rotated towards right and towards left once and then towards right once [14 rats ,4 rats, 1 rats, （P 〈 0.05 ）].③ The rotary circles in model group at the 45^th day were similar with that at the 10^th day [（526.10±173.96）, （538.52±187.88） circles per hour, （t=1.448, P 〉 0.05 ）]. CONCLUSION： ① The model rats have typical characteristics of neuroethology, mainly manifesting as original-place rotation by using its , uninjured side posterior limb as the fulcrum.② The models cannot be auto-recovery and is the stable and reliable model for studying PD.