紫杉醇暴露对秀丽隐杆线虫毒性效应的研究

Toxicity effects of paclitaxel exposure on Caenorhabditis elegans

目的:为了解紫杉醇的神经毒性机制,以秀丽隐杆线虫为模型进行运动能力和细胞凋亡的研究。方法:配制紫杉醇系列浓度(0.4、4、40、400 mg/L)为试验组溶液,以K-medium溶液为空白对照组(0 mg/L);秀丽隐杆线虫暴露于试验组和对照组溶液中,检测线虫运动行为及细胞凋亡水平的改变。结果:急性暴露后,与溶液对照组比较,试验组(0.4、4、40、400 mg/L)中线虫的运动能力均受到抑制。其中除0.4 mg/L实验组线虫头部摆动频率和身体弯曲频率(P<0.05),其他各实验组线虫的运动能力均明显下降(P<0.01),且与暴露浓度呈剂量-效应关系。与溶液对照组对比,经AO染色后的400 mg/L实验组线虫的细胞凋亡水平明显升高(P<0.01)。结论:紫杉醇溶液对线虫具有神经毒性,其暴露浓度与神经毒性呈相关关系,细胞凋亡可能是导致线虫神经毒性的作用机制之一。

Objective:To understand the neurotoxic mechanism of paclitaxel,Caenorhabditis elegans was used as a experimental model to study its motility and apoptosis.Methods:Paclitaxel diluted in different concentrations(0.4,4,40,400 mg/L)was prepared for the experimental groups,and K-medium solution as the blank control group.Then,Caenorhabditis elegans was exposed to the solution of the experimental groups and the blank control group,respectively.The effects of paclitaxel at different dose concentrations on the movement behavior of Caenorhabditis elegans and changes of apoptosis levels were evaluated to explore the toxicity of paclitaxel on Caenorhabditis elegans.Results:After acute exposure,the motility capacity of the Caenorhabditis elegans in the experimental groups(0.4,4,40,400 mg/L)was suppressed as compared with the blank control group.Among the experimental groups,only the 0.4 mg/L experimental group showed a decrease in the head swing frequency and body bending frequency(P<0.05),while the other experimental groups had a significant decrease in their motility capacity(P<0.01),and it showed a dose-response relationship with the concentration of exposure.Compared with the blank control group,the apoptosis level of Caenorhabditis elegans in the 400 mg/L experimental group was significantly increased after acridineorange(AO)staining(P<0.01).Conclusion:Paclitaxel solution has neurotoxic effects on Caenorhabditis elegans.Neurotoxicity is related to the dose concentration of paclitaxel.Apoptosis may be one of the mechanisms that lead to neurotoxicity in Caenorhabditis elegans.