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、1000、1500、2000 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1500 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。
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-35a2,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-35a2 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 1500 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.
作者
阮嘉莉
黄其春
RUAN Jiali;HUANG Qichun(Tumor Hospital Affiliated to Guangxi Medical University,Nanning 530021,China)
出处
《山东医药》
CAS
2020年第6期36-40,共5页
Shandong Medical Journal
基金
广西卫计委中医药科技专项项目(GZLC16-35)
广西卫生厅中医药课题(GZYZ-10-29)
关键词
地塞米松
生殖毒性
神经毒性
线虫
细胞凋亡
氧化胁迫相关基因
dexamethasone
reproduction toxicity
neurotoxicity
nematodes
apoptosis
oxidative stress-related genes