青霉素和红霉素对高脂处理小鼠葡萄糖和脂肪代谢的影响  

Effects of penicillin G and erythromycin on glucose and lipid metabolism in mice

作　　者：吴艳[1] 沈航杰 金萃媛 傅正伟[1] 靳远祥[1] 

机构地区：[1]浙江工业大学生物与环境工程学院,浙江杭州310032

出　　处：《毒理学杂志》2015年第5期338-343,共6页Journal of Toxicology

基　　金：国家自然科学基金(21107098);浙江省新苗人才计划(2014R403027)

摘　　要：目的探讨高脂饮食联合低剂量常用抗生素类药物长期暴露对小鼠葡萄糖和脂质代谢的影响。方法将4周龄的C57BL/6J雄性小鼠随机分成5组,每组8只,分别为高脂对照组(Con)、青霉素低浓度组(5 mg/L)(PL)、青霉素高浓度组(50 mg/L)(PH)、红霉素低浓度组(5 mg/L)(EL)、红霉素高浓度组(50 mg/L)(EH)。用高脂饲料联合药物处理90 d,并在75 d进行糖耐受试验。用HE染色法和油红O染色法观察肝脏组织的病理变化。检测血清游离脂肪酸(FFA)、葡萄糖(Glucose)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDLC),以及肝脏中TG的含量,并采用实时荧光定量PCR技术分析肝脏组织中PPARa和PPARg的基因表达水平的变化。结果抗生素药物处理组的肝脏组织切片显示明显的病理变化,肝脏细胞间脂质堆积明显增加,尤其是EH处理组。与高脂对照组相比,抗生素药物处理组的糖耐量异常,血清FFA、Glucose、TG上升(P<0.05),HDL-C呈下降趋势,无显著性。高浓度抗生素药物处理组肝脏中的TG含量和Pparg的表达量都显著高于对照组(P<0.05)。结论青霉素和红霉素低剂量长期暴露导致小鼠肝脏中脂质和糖代谢紊乱。Objective To study the effect of low dose of antibiotics chronic exposure on glucose and lipid metabolism in mice. Methods Four-week-old male C57BL/6J mice were randomly divided into five groups： high fat control group（Con） ,low dose of Penicillin G group （treated with Penicillin G 5 mg/L, PL）, high dose of Penicillin G group （treated with Penicillin G 50 mg/L, PH）, low dose of Erythromycin group （treated with Erythromycin 5 mg/L, EL）, high dose of Erythromycin group （treated with Erythromycin 50 mg/L, EH）. The exposure was lasted 90 days with high fat diet, and the intraperitoneal glucose tolerance test （GTF） was conducted in 75 days of treatment. HE staining and Oil red 0 staining were used to observe the liver pathological changes. Serum free fat acid （ FFA）, glucose, triglyceride （TG）, total cholesterol （TC） , low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C） and triglyceride （TG） in liver were also measured. Furthermore, quantitative （qRCR） real-time qPCR was used to investigate the transcriptional levels of PPARa and PPARg mRNA in the liver and fat. Results Pathological examination showed that lipid storage in the hepatocytes increased significantly in antibiotics treated groups, especially in the EH group. Compared with control group, the levels of FFA, Glucose, I＇G were increased （ P 〈 O. 05 ） significant in Penicillin G and Erythromycin treated groups. The level of HDL-C was decreased in antibiotics treatment groups, while no significant difference was observed. The antibiotics treatment groups within high dose appeared abnormal glucose tolerance. The TG level and mRNA expression of PPARg in the liver also significantly increased after exposure to two antibiotics （P 〈 3. 05 ）. Conclusion Penicillin G and Erythromycin with long-term administration can change the metanolism of lipid and glucose in the liver of mice.

关 键 词：青霉素 红霉素 肥胖 脂质代谢 葡萄糖代谢 小鼠 

分 类 号：R978.11[医药卫生—药品] R978.15[医药卫生—药学]