早期运动干预对PD大鼠模型感觉运动功能的影响

Effect of early exercise intervention on sensorimotor functions in PD rats

目的观察早期运动干预对帕金森病(Parkinson’s disease,PD)模型大鼠感觉运动功能障碍的影响,探索早期运动改善PD模型大鼠感觉运动功能障碍的影响。方法选取雄性清洁级SD大鼠随机分为对照安静组(SHAM-S),对照运动组(SHAM-E),PD安静组(PDS),PD运动组(PDE)。采用内侧前脑束(medial forebrain bundle,MFB)注射神经毒素6-羟基多巴胺(6-hydroxydopamine,6-OHDA)的方法建立偏侧PD大鼠模型。4周跑台运动训练于术后24 h进行,大鼠造模后每7 d进行圆筒测试、网格测试检测行为学功能,造模后第14、28天检测纹状体(striatum,Str)内酪氨酸羟化酶(tyrosine hydroxylase,TH)的含量。结果(1)PDS组大鼠患侧Str TH细胞阳性数量显著降低,且随时间逐步减少;PDE组大鼠患侧Str TH细胞阳性数量显著提升,随时间无显著变化。(2)PDS组大鼠圆筒测试得分显著增加,随时间无显著变化;PDE组大鼠1、4、7、11、14 d测试得分无统计学意义,21、28 d的得分显著减少,有较明显的左前肢活动恢复现象存在。(3)PDS组大鼠网格实验患侧前肢掉落次数显著增加,随时间无显著变化;PDE组大鼠患侧前肢掉落次数显著下降,且随时间显著降低。(4)PDS组大鼠在各测试时间点的行进格数和总步数均显著下降,且随着时间呈显著下降趋势;PDE组大鼠在第4天开始显著上升,且随时间无显著变化。结论偏侧MFB注射6-OHDA大鼠模型存在感觉运动与自主运动功能障碍。早期介入跑台运动有助于抑制黑质-纹状体多巴胺能神经元的丢失,改善PD模型大鼠的感觉运动功能障碍,且运动干预效果随时间的延长增强。

Objective To observe the effect of early exercise intervention on motor dysfunction in a Parkinson's disease(PD)model in rats,and to explore the cumulative effect of early exercise on improving motor dysfunction.Methods Male specific pathogen-free SD rats were randomly divided into four groups:sham-operated quiet(SHAM-S),sham-operated exercise(SHAM-E),PD quiet(PDS),and PD exercise(PDE)groups.A unilateral PD rat model was established by injecting 6-hydroxydopamine(6-OHDA)into the right medial forebrain bundle(MFB)of rats.The exercise group started running on a treadmill at 24 hours after surgery.Rats were assessed for behavioral functions using cylindrical and grid tests every 7 days after modeling.Tyrosine hydroxylase(TH)content in striatum(Str)was assessed by immunohistochemistry and western blotting on days 14 and 28 after modeling.Results(1)The number of TH+cells in Str on the affected side of PD model rats was significantly decreased and then gradually decreased over time.The number of TH+cells in Str on the affected side of PDE group rats was significantly increased,but there was no significant change over time.(2)The cylinder test score of PD model rats was significantly increased,but there was no significant change over time.In the PDE group,no statistically significant difference was found in test scores on days 1,4,7,11,and 14.However,the scores were significantly decreased on days 21 and 28,indicating significant recovery in left forelimb activity.(3)The number of forelimb drops on the affected side was significantly increased in the PDS group,but did not show any significant change over time.Conversely,the number of forelimb drops on the affected side of PDE group rats was significantly decreased and continued to decrease over time.(4)Additionally,the number of grids and total steps of PDS group rats were significantly decreased at each time point,exhibiting a significant downward trend over time.Conversely,PDE group of rats showed a significant increase starting from day 4 and did not show any significant change over time.Conclusion Unilateral MFB injection of 6-OHDA into rats leads to motor dysfunction.Early exercise intervention effectively improves the motor dysfunction of PD model rats,while also suppressing the decrease in dopamine content in the substantia nigra striatum.Moreover,the effect of exercise intervention increases over time.