左旋多巴对帕金森病模型大鼠结肠酪氨酸羟化酶和α-突触核蛋白表达的影响

Effects of L-dopa on colon tyrosine hydroxylase and a-synuclein expression of rats model of Parkinson disease

目的探讨左旋多巴(L-dopa)对帕金森病(PD)模型大鼠结肠酪氨酸羟化酶(TH)及α-突触核蛋白(α-Syn)表达的影响。方法健康SD大鼠72只随机分为对照组、帕金森病模型组(模型组)、左旋多巴治疗组(治疗组),各组随机再分为模型制备成功后4 d、8 d 2个亚组,各12只。采用大鼠颈背部皮下注射鱼藤酮制备帕金森病模型,免疫组化法和Western blotting蛋白印迹法检测结肠TH和α-Syn表达水平。结果 1 h粪便排出量及含水量:与对照组比较,模型组、治疗组大鼠显著降低(P<0.05);与模型组比较,治疗组大鼠增加(P<0.05);与治疗4 d亚组比较,治疗8 d亚组增加(P<0.05)。免疫组化法与Western blottng检测TH、α-Syn比较:(1)与对照组比较,模型组、治疗组各时间点结肠TH阳性细胞及蛋白表达均明显减少,α—Syn阳性细胞及蛋白表达均明显增加(P均<0.05);(2)与模型组比较,治疗组各时间点结肠TH阳性细胞及蛋白表达均增多,α—Syn阳性细胞及蛋白表达均明显减少(P均<0.05);(3)与治疗4 d亚组比较,治疗组治疗8 d亚组的TH阳性细胞及蛋白表达升高(P<0.05),α—Syn阳性细胞及蛋白降低(P<0.05)。结论 PD模型大鼠结肠功能障碍的机制可能与多巴胺的减少及α—Syn水平的增多有关,左旋多巴可能通过增加多巴胺和减少α—Syn水平改善PD大鼠结肠功能障碍。

Objective To investigate the effect of levodopa （L-dopa） on Parkinson＇s disease （PD） rats colon tyrosine hydroxylase（TH）andtheexpressionofalpha-synuclein（ɑ-Syn）.Methods 72healthySDratswererandomlydividedinto control group, model of PD group （model group）,L-dopa treatment group （treatment group）, each group was subdivided into the successful preparation of the model after 4 d, 8 d and 2 sub-groups, 12 rats in each group.Preparation of PD model rats were performed with subcutaneous injection of rotenone , immunohistochemistry and Western blotting blot were used to detect thecolonicTHandɑ-Synexpressionlevel.Results 1hfecaloutputandwatercontent：comparedwithcontrolgroup,therats in model group and the treatment group decreased significantly （ P 〈0.05）; compared with the model group, rats in the treatment group were increased （ P 〈0.05）; and compared with the treatment 4 d subgroups, treatment 8 d group was increased （ P 〈0.05）.（1）Compared with the control group, model group and treatment group at each time point , colon TH positive cells and protein expression were significantly reduced , the expression of ɑ-Syn positive cells and protein were significantly increased （ P 〈0.05）;（2）Compared with the model group, the treatment group at each time point, colon TH positive cells and protein expression were increased , the expression of ɑ-Syn positive cells and protein was significantly reduced （ P 〈0.05）;（3）Compared with the 4 d treatment group, TH positive cells and protein expression was elevated in 8 d treatment subgroups （ P 〈0.05）,ɑ-Syn positive cells and protein were decreased （ P 〈0.05）.Conclusion The mechanism of PD model rat colonic dysfunction may related with reduced dopamine and increased ɑ-Syn level,L-dopa may by increasing dopamine and reduce the level of ɑ-Syn thus improve colonic dysfunction in PD rats .