论文部分内容阅读
目的研究肌苷对Tourette综合征(TS)大鼠脑组织多巴胺D2受体(DRD2)和多巴胺转运蛋白(DAT)的影响,探讨肌苷治疗TS可能的作用机制。方法将40只SPF级雄性SD大鼠随机分为正常对照组、模型组、阳性对照组(氟哌啶醇0.5 mg·kg-1)、联合用药组(氟哌啶醇0.25 mg·kg-1+肌苷320 mg·kg-1)、肌苷组(肌苷320 mg·kg-1),每组8只。采用亚氨基二丙腈(IDNP)腹腔注射法建立TS大鼠模型。氟哌啶醇和(或)肌苷给药28 d后通过大鼠刻板行为评分、酶联免疫吸附法、原位杂交法,研究肌苷对TS模型大鼠刻板行为、大鼠脑组织DRD2、DAT水平的影响以及DRD2 mRNA表达情况。结果 1.肌苷组大鼠刻板行为评分低于模型组(P<0.01),高于阳性对照组(P<0.01),与联合用药组之间比较差异无统计学意义(P>0.05)。2.DRD2阳性细胞广泛分布于大脑皮质、海马、纹状体等处,以模型组DRD2阳性细胞分布最为密集。3.肌苷组DRD2水平低于模型组(P<0.01),高于阳性对照组和联合用药组(Pa<0.01),而与正常对照组之间比较差异无统计学意义(P>0.05)。4.肌苷组DAT水平高于正常对照组、模型组及阳性对照组(Pa<0.01),与联合用药组之间比较差异无统计学意义(P>0.05)。结论肌苷改善TS模型大鼠的刻板行为的作用机制可能是通过促进多巴胺释放和转运,起到类似于DRD2拮抗剂的作用。
Objective To study the effects of inosine on dopamine D2 receptor (DRD2) and dopamine transporter (DAT) in the brain of Tourette syndrome (TS) rats and to explore the possible mechanism of inosine treatment of TS. Methods Forty SPF male Sprague-Dawley rats were randomly divided into normal control group, model group and positive control group (haloperidol 0.5 mg · kg -1), combined with 0.25 mg · kg -1 haloperidol + Inosine 320 mg · kg-1) and inosine group (inosine 320 mg · kg-1), 8 in each group. TS rat model was established by intraperitoneal injection of iminodipropionitrile (IDNP). After 28 days of administration of haloperidol and / or inosine, stereotypic behavior score, enzyme-linked immunosorbent assay and in situ hybridization were used to study the effect of inosine on the stereotyped behavior of rat TS model, DRD2, DAT Level of influence and DRD2 mRNA expression. The results showed that the stereotypic scores of inosine group were lower than that of model group (P <0.01), higher than that of positive control group (P <0.01), but there was no significant difference between them (P> 0.05). DRD2-positive cells are widely distributed in the cerebral cortex, hippocampus, striatum and other places, the model group DRD2-positive cells are most densely distributed. The level of DRD2 in the inosine group was lower than that in the model group (P <0.01), higher than that in the positive control group and combination group (Pa <0.01), but no significant difference compared with the normal control group (P> 0.05) . The DAT level in inosine group was higher than that in normal control group, model group and positive control group (Pa <0.01), but there was no significant difference between them (P> 0.05). Conclusions Inosine can improve the stereotypic behavior of TS model rats by acting as a DRD2 antagonist by promoting dopamine release and transport.