尼古丁抑制6-羟基多巴胺损伤诱导的CD8^+T淋巴细胞浸润

Nicotine inhibit the recruitment of CD8 lymphocytes produced by 6-hydroxydopamine lesion in the striatum of SD rat

目的:采用6-羟基多巴胺部分损伤大鼠帕金森病模型,探讨尼古丁保护多巴胺能神经元的机制。方法:动物分别接受尼古丁(0.2mg/kg或2.0mg/kg)或生理盐水腹膜腔内注射。注射7天后,尼古丁高、低剂量治疗组和模型对照组动物分别接受纹状体内6-OHDA20μg注射,制作部分损伤帕金森病模型。免疫组织化学及体视学方法定量分析黑质多巴胺能神经元和纹状体CD8+T淋巴细胞数量。结果:尼古丁低剂量治疗组和高剂量治疗组,6-OHDA注射侧的酪氨酸羟化酶免疫阳性细胞分别为相应对照侧的64.97±10.33%和67.24±12.67%;和模型对照组(25.27±11.79%)比较,差异有统计学意义(P<0.01)。此外,尼古丁也可明显减少纹状体CD8+T淋巴细胞浸润(P<0.05)。结论:尼古丁可能通过抑制CD8+T淋巴细胞浸润,保护多巴胺能神经元。

Objective： To explore the mechanism through which nicotine protects dopaminergic neurons against 6-OHDA toxicity in SD rat PD model. Methods： Rats received nicotine or saline treatment （two doses tested,0.2 mg/ kg and 2 mg/ kg, 5 injections i.p. per day at 2-h intervals）. 8 days after the treatment, a single injection of 20μg 6-OHDA was administered into striatum. Nicotine or saline was administered daily until animals were sacrificed. The dopaminergic neurons and CD8-positive lymphocytes were analyzed quantitatively using immunohistochemistry and stereology. Results： The loss of dopaminergic neurons induced by 6-OHDA in the substantia nigra was significantly less severe in the nicotine treatment groups （at both 0.2 and 2 mg/kg groups） than in the saline treated group（P〈0.01）. In addition, the number of CD8-positive lymphocytes reduced significantly in the nicotine treated animals as compared to saline control（P〈0.05）. Conclusion： Our data suggest that nicotine may have a neuroprotective effect against 6-OHDA induced dopaminergic lesion by inhibiting the recruitment of CD8-positive lymphocytes.