雷公藤内酯醇对脂多糖诱导黑质多巴胺能神经元变性的保护作用

目的观察雷公藤内酯醇（triptolide，Tri）对脂多糖（lipopolysaccharide，LPS）诱导黑质多巴胺能（dopamine，DA）神经元变性的保护作用。方法40只大鼠随机分为4组，每组10只，即：假手术对照组，LPS模型组，LPS加Tri组，LPS加生理盐水组。14天后观察LPS和雷公藤内酯醇对阿朴吗啡诱发的旋转行为、大鼠毁损侧纹状体DA及其代谢产物的含量和DA合成限速酶酪氨酸羟化酶（tyrosine hydroxylase，TH）阳性细胞数及小胶质细胞激活情况的影响。结果黑质注射LPS后可以模拟脑部免疫炎症反应异常现象，导致DA能神经元变性；黑质注射LPS后引起大鼠向注射侧出现旋转，雷公藤内酯醇能抑制这一作用；并能明显保护纹状体DA及其代谢产物的含量的降低及TH阳性细胞数的减少，抑制小胶质细胞的激活（P〈0．01）。结论雷公藤内酯醇可以通过抑制小胶质细胞激活，保护炎性介导的DA能神经元变性。

Protective Effects of Triptolide on the Lipopolysaccharide-mediated Degeneration of Dopaminergic Neurons in Substantia Nigra

ObjectiveTo study the protective effects of triptolide (Tri) on the lipopolysaccharide (LPS)-mediated degeneration of dopaminergic neurons in substantia nigra. MethodsForty SD rats were randomly divided into four groups: the sham group, the LPS model group, the Tri group and the normal saline group, 10 in each group. Fourteen days later, the apomorphine-induced rotational behavior, the content of dopamine (DA) and its metabolites in the striatum of the injured side, the number of tyrosine-hydroxylase (TH) positive neurons and activation of microglia in rats were observed. ResultsInjection of LPS in substantia nigra could induce cerebral simulated immunoinflammatory reaction, leading to degeneration of dopaminergic neuron and induce ipsilateral directed rotational behavior of rats, which could be improved by Tri. Moreover, Tri could raise the lowered content of DA and its metabolites as well as the TH positive neurons in striatum, and suppress the activation of microglia significantly (P<0.01). ConclusionTri could protect the dopaminergic neurons from degeneration due to the inflammation mediated by LPS through inhibiting the activation of microglia.