| Carbendazim(CBZ)is a broad-spectrum benzimidazole fungicide,widely used in the prevention and treatment of fungal diseases.The mass production and use of CBZ have led to more and more residues so that many reports have proven its harmfulness to organisms.Moreover,CBZ is considered to be an endocrine disruptor that may be toxic to different target organs in mammals.Endocrine disruptors are considered to be one of the main causes of obesity because they can break the body’s lipid metabolism balance and induce fat accumulation.However,there are few studies on obesity caused by CBZ with lipid metabolism disorder of the body,and its mechanism of action is not clear.This thesis was taken CBZ as the research object and C.elegans as the model organism to explore the effect and mechanism of CBZ on the physiology and biochemistry of C.elegans,and further studied the effects of CBZ on the fat accumulation and lipid metabolism mechanism of nematodes on this basis.The main contents and results are as follows:1.The effects of exposure to different concentrations of carbendazim on the physiology and biochemistry of C.elegans were studied.By studying the head thrashing,body bending,body length and body surface area,the number of offspring,life span,reactive oxygen species(ROS)and superoxide dismutase activity(SOD)of C.elegans exposed to low concentrations of carbendazim,the effects of carbendazim on the endocrine system of C.elegans was preliminarily determined.The results showed that when the concentration of carbendazim was higher than 0.01 μg/L,the neurotoxicity,reproductive toxicity and oxidative stress of C.elegans had a negative impact,and further shortened the lifespan of C.elegans.2.The effects of CBZ on the fat deposition of C.elegans were studied.Preliminary evaluations were made on fat deposition and gene regulation mechanism of C.elegans exposed to CBZ by measuring the degree of oil red O(ORO)staining,triglycerides(TG),free fatty acids(FFA),the fat content of genetic defect mutant nematodes related to lipid metabolism and fluorescent-labeled protein nematodes,etc.The results showed that when the concentration of carbendazim was 1 μg/L,ORO,FAA,and TG contents of C.elegans increased significantly.Besides,CBZ may induce C.elegans fat deposition through the daf-2-mediated insulin signaling pathway and nhr-49 mediated nuclear hormone signaling pathway inhibiting the energy consumption(AAK-2),lipid hydrolysis(ATGL-1)and promoting lipid desaturation(Fat-5,Fat-6 and Fat-7)and β-oxidation(ACS-2)of C.elegans.3.The effects of CBZ on the metabolites of C.elegans and its mechanism were studied.Based on lipidomics analysis,through the analysis and identification of the differential metabolites of C.elegans exposed to 1 μg/L CBZ,the expression levels of 119 metabolites were significantly up-regulated and 114 expression levels were significantly down-regulated.The content of glycerides and phosphate metabolites was relatively high.Besides,the key metabolic pathways involved in these differential metabolites were glycerophospholipid metabolism,α-linolenic acid metabolism,arachidonic acid metabolism,glycerolipid metabolism,and glycosylphosphatidylinositol(GPI)-anchored biosynthesis,among which glycerophospholipid metabolism pathway contributes the most,mainly regulating the expression of PC,DAG,PE,TAG and Acyl Glc PC with key metabolic enzymes named the acyltransferase and phosphatidylserine decarboxylase the in this process. |
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