大鼠脑黑质区注射LPS致多巴胺能神经元及血清TNF-α的变化

Changes in dopaminergic neurons and serum TNF-α of rats following intranigral injection of LPS

目的研究脂多糖（LPS）对黑质多巴胺（DA）能神经元的毁损情况及其与血清肿瘤坏死因子α（TNF—α）水平之间的关系。方法向大鼠右侧黑质立体定位注射LPS或PBS后，用免疫组化法观察DA能神经元的损伤状况，用放射免疫法测定血清TNF-α水平。结果LPS注射后24h右侧黑质酪氨酸羟化酶（TH）阳性神经元较左侧显著减少（P〈0．001），14d达到最低点，14～28d没有明显改变；血清TNF-α水平在LPS组24h、14d和28d显著高于对照组（P〈0．01）；LPS组大鼠的黑质TH阳性神经元存留率与其血清TNF-α水平之间存在负直线相关（P〈0．05）。结论LPS注入黑质能诱导DA能神经元变性、血清TNF-α水平升高，且两者之间存在负直线相关。

Objective To study the degeneration of dopaminergic neurons and its relationship with level of TNF-α in serum by intranigral injection of LPS. Methods LPS or PBS was stereotaxically injected into substantia nigra （SN）. At different survival times, the damage to the substantia nigral DA neurons was observed by using tyrosinehydroxylase immunohistochemical staining and the level of TNF-α in serum was measured by Radioimmunoassay. Results Tweenty-four hours after LPS injection, there was apparent reduction in TH-positive cells on the LPS-injected side. The decrease reached its peak after 14 days. In the subsequent days, the degree of degeneration remained at the stage. Differences were found when compared to the level of TNF-α in serum of 24 h,14 d and 28 d with that of the control group. The former was higher. The study showed a linear correlation between the level of TNF-α and the survival rate （ percentage of right TH-positive neurons to left）. Conclusion Intranigral injection of LPS can significantly induce dopaminergic neurons degeneration and TNF-α increase in serum. The level of TNF-α in serum is related to the degeneration of dopaminergic neuron in substantia nigra.