脑源性神经营养因子对左旋多巴诱发的帕金森病异动症大鼠行为的影响及其作用机制

发布时间：2018-06-05 06:52

本文选题：帕金森病 + 异动症　；参考：《临床神经病学杂志》2017年01期

【摘要】：目的探讨脑源性神经营养因子(BDNF)对左旋多巴(L-DOPA)诱发异动症大鼠行为的影响及其作用机制。方法建立单侧毁损帕金森病(PD)大鼠模型,随机分为L-DOPA组、L-DOPA+BDNF组、BDNF组及生理盐水组。L-DOPA组及L-DOPA+BDNF组腹腔注射L-DOPA 25 mg/kg+苄丝肼6.25 mg/kg,BDNF组及生理盐水组腹腔注射等体积的生理盐水,2次/d,连续注射21 d。L-DOPA+BDNF组及BDNF组大鼠右侧纹状体立体定位注射BDNF(1μg/4μl),L-DOPA组及生理盐水组大鼠右侧纹状体立体定位注射生理盐水(4μl)。L-DOPA组和L-DOPA+BDNF组大鼠在纹状体注射后继续腹腔注射L-DOPA 7 d。在第2、11、21、23和29 d进行进行异常不自主运动(AIM)评分及跨步实验。应用Western blot技术检测大鼠脑纹状体组织Trk B磷酸化水平。结果生理盐水组及BDNF组大鼠未出现不自主运动。L-DOPA组和L-DOPA+BDNF组第2、11、21 d的AIM评分差异无统计学意义。与L-DOPA组比较,L-DOPA+BDNF组大鼠第23 d的肢体、轴性、口舌AIM评分及29 d的轴性、口舌AIM评分均显著降低(均P0.05)。生理盐水组和BDNF组大鼠各时间点注射前后左前肢跨步数无改变。与注射前比较,L-DOPA组及L-DOPA+BDNF组大鼠各时间点注射后左前肢跨步数均显著增加(均P0.05)。4组大鼠的左前肢跨步数在治疗过程中均呈下降趋势。与L-DOPA组和生理盐水组相比,L-DOPA+BDNF组和BDNF组的毁损侧纹状体p Trk B蛋白表达水平增加(均P0.05)。BDNF组和L-DOPA+BDNF组两组之间及L-DOPA组和生理盐水组两组间的p Trk B蛋白表达水平差异无统计学意义。各组间健全侧纹状体的p Trk B蛋白表达水平差异无统计学意义。4组间Trk B水平差异无统计学意义。结论外源给予BDNF能够改善L-DOPA诱导的异常不自主运动,并且不影响L-DOPA抗PD的运动疗效,其机制可能与激活BDNF-Trk B信号通路有关。
[Abstract]:Objective to investigate the effect of brain-derived neurotrophic factor (BDNF) on the behavior induced by L-DOPA in rats with dyskinesia. Methods unilateral lesion of Parkinson's disease (PD) rat model was established. They were randomly divided into L-DOPA group, L-DOPA BDNF group and normal saline group. L-DOPA group and L-DOPA BDNF group were injected intraperitoneally with L-DOPA 25 mg/kg benzylhydrazine 6.25 mg / kg BDNF group and normal saline group by intraperitoneal injection of the same volume of normal saline twice a day. The rats of 21 d.L-DOPA BDNF group and BDNF group were injected continuously. The right striatum was injected with BDNF(1 渭 g / 4 渭 L L-DOPA group and saline group. The right striatum group and L-DOPA BDNF group were injected intraperitoneally with L-DOPA 7 days after striatum injection. The AIMs of abnormal involuntary movement were scored and stride tests were carried out on the 23rd and 29th day at the 2nd day of 11 ~ (th) ~ (th) day. The level of Trk B phosphorylation in rat striatum was detected by Western blot technique. Results there was no significant difference in AIM scores between the saline group and the BDNF group. Compared with L-DOPA group, the limb, axis, oral AIM score and 29 day AIM score of rats in L-DOPA BDNF group were significantly lower than those in L-DOPA BDNF group on the 23rd day (P 0.05). There was no change in the number of steps of left forelimb before and after injection in saline group and BDNF group. Compared with those before injection, the number of left forelimb stride increased significantly in L-DOPA group and L-DOPA BDNF group at each time point after injection (all P0.05.4 rats showed a downward trend in the course of treatment. Compared with L-DOPA group and normal saline group, the expression of p Trk B protein in injured striatum increased in L-DOPA BDNF group and BDNF group (both P0.05).BDNF group and L-DOPA BDNF group, L-DOPA group and normal saline group). The expression level of p Trk B protein was lower in both P0.05).BDNF group and L-DOPA BDNF group, and between L-DOPA group and normal saline group. There was no statistical significance. There was no significant difference in the expression of p Trk B protein in healthy striatum between groups. 4. There was no significant difference in Trk B level among groups. Conclusion exogenous BDNF can improve the abnormal involuntary movement induced by L-DOPA and does not affect the effect of L-DOPA on PD. The mechanism may be related to the activation of BDNF-Trk B signaling pathway.
【作者单位】：苏州大学附属第二医院神经内科;
【基金】：国家自然科学基金(81200970)
【分类号】：R742.5

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