多菌灵暴露对发育期小鼠糖脂代谢的干扰效应及作用通路OA

Objective:To explore the disrupting effects of low-dose methyl-2-benzimidazole carbamate(CBZ)on glycolipid metabolism in mice during pubertal development period and its mechanism.Methods:A developmental(4-week-old)and adult(8-week-old)ICR mouse model with low-dose CBZ exposure was established.The mice were randomly divided into a blank control group(administered with corn oil)and different dose CBZ exposure groups(0.3,3,30 and 60 mg/kg),and were given intragastric administration for 28 days.Commercial kits were used to detect the serum levels of total cholesterol(TC),total triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),creatinine(CRE),blood urea nitrogen(BUN),aspartate aminotransferase(AST),alanine aminotransferase(ALT),as well as the activity of glucose-6-phosphate dehydrogenase(G6PD)in the liver.Fasting blood glucose(FBG)was measured by a blood glucose meter.Body weight was monitored by weighing.The expression levels of genes related to glycolipid metabolism and endoplasmic reticulum stress pathway were detected by quantitative real-time PCR.Results:Compared with the blank control group,CBZ exposure significantly increased the serum lipid levels and various blood biochemical indexes in developing and adult mice(P＜0.05 or P＜0.01),and only significantly increased the FBG level in adult mice(P＜0.05 or P＜0.05),while high-dose CBZ exposure markedly reduced the body weight of adult mice(P＜0.05).CBZ exposure up-regulated the expression of lipid synthesis and transport genes such as CD36 and SREBP-1,down-regulated the expression of lipid metabolism genes such as PPARα and HNF4α,as well as gluconeogenesis and glycogen synthesis genes such as G6PC,PEPCK and GSK-3β in developing and adult mice(P＜0.05).Meanwhile,CBZ up-regulated the expression of GRP78,PERK,CHOP,Bax,Caspase-3 and other genes(P＜0.05),down-regulated the expression of ATF4 and Bcl-2 genes(P＜0.05),and activated the endoplasmic reticulum stress and apoptotic pathways.Conclusion:CBZ exerts endocrine and metabolic toxicity to developing mice,which can interfere with glycolipid metabolism and cause metabolic dysfunction by affecting the expression of glycolipid metabolism-related genes and activating the endoplasmic reticulum stress signaling pathway.