【摘要】 目的探讨地塞米松对秀丽隐杆线虫的毒性效应及其机制。方法将秀丽隐杆线虫分别暴露在终浓度为0、500、1 000、15 00、2 000 mg/L地塞米松溶液(空白组、D1组、D2组、D3组、D4组)中48 h后,观察秀丽隐杆线虫的生殖能力、运动能力;吖啶橙AO染色法观察细胞凋亡程度;实时荧光定量PCR检测部分氧化胁迫相关基因[超氧化物歧化酶基因(Sod-1)、类P-53蛋白基因(Cep-1)、细胞色素P450家族蛋白基因(Cyp-35a2)、谷胱甘肽转移酶基因(Gst-1)]。结果与空白组相比,D2、D3、D4组线虫产卵数下降(P均<0. 01); D4组线虫头部摆动、身体弯曲能力、咽泵频率降低(P均<0. 01)。秀丽隐杆线虫的细胞凋亡程度随着地塞米松浓度的升高而加重(P均<0. 05)。与空白组比较,D1、D2、D3、D4组线虫体内Sod-1基因相对表达量升高(P均<0. 01);与空白组比较,D1、D2组线虫体内Cep-1基因相对表达量升高,D3、D4组又降低(P均<0. 05);与空白组比较,D1组Cyp-35a2基因相对表达量降低,D2、D3、D4组升高但无统计学意义;与空白组比较,D1、D2、D3、D4组Gst-1的相对表达量均降低(P均<0. 01)。结论 1 500 mg/L浓度及以上的地塞米松对秀丽隐杆线虫具有明显的生殖、神经毒性,可能与其引起氧化应激反应和促使细胞凋亡有关。更多还原

【Abstract】 Objective To observe the various toxic effects of dexamethasone on Caenorhabditis elegans(C. elegans)and to elucidate the mechanism. Methods The nematodes were exposed to dexamethasone solution at different concentrations of 0,500,1000,1500,and 2000 mg/L(blank group,and groups D1,D2,D3,D4) for 48 hours. After exposure,the physiological level(reproductive rate,exercise capacity) of C. elegans was detected; the acridine orange AO staining method was used to detect the degree of apoptosis,while real-time fluorescent quantitative PCR was used to detect some stress-related genes(superoxide dismutase gene Sod-1,apoptosis-related gene Cep-1,P450 family protein gene Cyp-35 a2,and glutathione transferase gene Gst-1). Results Compared with the blank group,the number of spawning of nematodes in the groups D2,D3,and D4 decreased(P < 0. 01); the head swinging,body bending ability,and throat pump frequency of the group D4 were lower(all P < 0. 01). The apoptosis of C. elegans increased with the increase of the exposure concentration(all P < 0. 05). Compared with the blank control group,the expression levels of Sod-1 in the groups D1,D2,D3,and D4 increased(all P < 0. 01). Compared with the blank group,the relative expression of Cep-1 gene in nematodes of groups D1 and D2 increased,but the expression of groups D3 and D4 decreased(all P < 0. 05). Compared with the blank group,the relative expression of Cyp-35 a2 gene in the group D1 group decreased,which in the groups D2,D3,and D4 increased,but there was no statistical significance; the relative expression of the Gst-1 in the groups D1,D2,D3,and D4 decreased(all P <0. 01). Conclusion Dexamethasone at a concentration of 1 500 mg/L and above has obvious physiological toxicity to C. elegans,and its mechanism of action may be related to causing oxidative stress and promoting apoptosis.更多还原