利福平对鱼藤酮诱导大鼠的抗多巴胺神经元凋亡作用

目的探讨利福平抗鱼藤酮诱导帕金森病大鼠模型多巴胺神经元凋亡的作用。方法给SD大鼠背部皮下注射鱼藤酮1.5 mg/(kg.d)3周使其黑质多巴胺神经元发生凋亡,同时经灌胃给予利福平30 mg/(kg.d)干预,并通过对大鼠中脑切片进行TUNEL及Bax、Bcl-2和Caspase-3的免疫活性检测以明确利福平抗多巴胺神经元凋亡的作用。结果长期低剂量接触鱼藤酮可诱导SD大鼠中脑黑质部位出现凋亡细胞增加以及Bax、Bcl-2、Caspase-3的免疫活性的改变(P均<0.01),而应用利福平后可明显减轻这些变化(P均<0.01)。结论利福平具有抗鱼藤酮帕金森病大鼠模型的多巴胺神经元凋亡的作用,且此作用是通过上调Bcl-2和Bax的比值、抑制caspase通路而实现的。

The protective effects of rifampicin against rotenone-induced apoptosis in rats

Objective To investigate the protective effects of rifampicin against rotenone-induced apoptosis in rats.Methods Chronic subcutaneous exposure to rotenone at 1.5 mg/(kg·d) caused highly selective apoptosis in the nigrostriatal dopaminergic neurons in rats.Rifampicin was administered at 30 mg/(kg·d) by intragastric administration and its effects of inhibiting rotenone-induced apoptosis were assessed by TUNEL and Immunoactivity detection of Bax,Bcl-2 and Caspase3.Results Chronic subcutaneous exposure to rotenone could cause highly selective apoptosis in the nigrostriatal dopaminergic neurons in rats(P < 0.01) whereas rifampicin could significantly reduced rotenone-induced apoptosis(P < 0.01).Conclusions The present study demonstrates that rifampicin can protect dopaminergic neurons against apoptosis by inhibiting caspase pathway and triggering Bcl-2 gene,suggesting the therapeutic prospect of rifampicin to Parkinson’s disease.