典型抗生素对羊角月牙藻的生长抑制及其联合毒性

Growth inhibitive effect of typical antibiotics and their mixtures on Selenastrum capricornutum

目的研究两种使用量较大的头孢类抗生素（头孢氨苄、头孢拉定）及其主要降解产物7-氨基头孢霉烷酸（7-ACA）和四环素类药物（四环素和金霉素）对羊角月牙藻（Selenastru mcapricornutum）生长的作用及其联合毒性。方法将5种物质分别暴露于羊角月牙藻，设置5个浓度梯度（四环素和金霉素均为0．25～4μg／ml，头孢氨苄、头孢拉定均为0．1-1000μg／ml，7-ACA为60～960μg／m1）及空白对照；同时，依据毒性单位法设计四环素＋金霉素及四环素＋7-ACA的联合毒性实验，5个浓度梯度的混合物总毒性单位（TU）为0．2、0．4、0．8、1．6和3．2TU，培养72h后测定藻液密度并计算相应抑制率和半数抑制浓度（IC50值）。结果羊角月牙藻的72h—IC50分别为：四环素0．50μg／ml、金霉素0．47μg／ml、7-ACA775．6μg／ml。头孢拉定在测试浓度范围（0．1～1000μg／m1）的抑制率均为负值；头孢氨苄在低浓度（0．1、1和10μg／m1）时的抑制率为负值，但在高浓度（100和1000μg／m1）下产生抑制作用；且当头孢氨苄浓度为1000μg／ml时，抑制率小于50％。因而头孢拉定和头孢氨苄在所测试范围内不能计算出72h—IC50值。四环素＋金霉素组的IC50值为0．99TU；而四环素＋7-ACA组的IC50值为1．5TU50结论四环素类药物对羊角月牙藻的生长产生抑制作用；但头孢拉定在测试浓度却刺激羊角月牙藻的生长；头孢氨苄和7-ACA对羊角月牙藻的作用存在明显hormesis现象，且7-ACA的毒性明显高于其母体。四环素和金霉素的联合毒性表现为相加作用，而四环素＋7-ACA的联合毒性则为拮抗作用。

Objective To study the effects of two commonly used cephalosporins （cephalexin,cefradine） and their main degradation product 7-aminocephalosporanic acid （7-ACA）, and two widely used tetracycline drugs （tetracycline, chlortetracycline） ,on the growth of Selenastrum capricornutum and the joint toxicity. Methods Selenastrum capricornutum was exposed respectively to the five compounds at five different concentrations （0.25-4 μg/ml for tetracycline and chlortetracycline,0.1-1 000 μg/ml for cephalexin and cefradine,60-960 μg/ml for 7-ACA）, and a control group without compounds was set. In addition,according to toxicity unit method,the joint toxicity tests of tetracycline ＋aureomycin and tetracycline＋7-ACA were set at five concentrations of 0.2,0.4,0.8,1.6 and 3.2 TU. After treatment for 72 h,the density of the algae population was measured. The percent of growth inhibition and median inhibitory concentration （IC50 value） were calculated. Results The 72 h-IC50 values of tetracycline,chlortetracycline and 7-ACA for Selenastrum capricornutum were 0.50,0.47 and 775.6 μg/ml,respectively. The percent of growth inhibition of cefradine was negative at each tested concentration （0.1-1 000 μg/ml）. However,the growth of the algae was stimulated by cephalexin at lower concentrations （0.1,1 and 10 μg/ml）, but inhibited by eephalexin at higher concentrations （ 100 and 1 000 μg/ml）. The inhibition percent of eephalexin at 1 000 μg/ml was less than 50%. Therefore,the 72 h-IC50 values of cefradine and cephalexin could not be calculated in the tested concentration range. For the mixture toxicity,IC50 values of tetracycline ＋aureomycin group and tetracycline＋7-ACA group were 0.99 TU and 1.5 TU,respectively. Conclusion The tetracycline drugs may inhibit the growth of Selenastrum capricornutum while cefradine may have stimulation at the tested concentrations. Cephalexin and 7-ACA presented hormesis. The toxicity of eephalosporin antibiotics degradation product 7-ACA was obviously higher than that of its parents. Combined effects of antibiotics on Selenastrum capricornutum were found to be additive for tetracycline＋aureomycin and antagonistic for tetracvcline＋7-ACA.