Toxic Effects And Mechanisms Of Cadmium On BV2 Microglia

Cadmium is a kind of toxic heavy metal that is widely spread in the environment.Cadmium can damage the internal organs such as liver,kidney,lung and spleen,and leads to metabolism dysfunction in many cells.Cadmium is also a potential pathogenic factor of many diseases.Microglia is a kind of immunocyte in central nervous system.Under pathological conditions,microglia will be activated and participate in inflammatory process by secreting cytokines associated with inflammation,and play a role in cell repairation and cell apoptosis.Beyond that,microglia will also phagocytose necrotic cells and cell debris.Cadmium enters the body through various means such as inhaling and diet,to exert its effedt on the central nervous system.It is a serious threat to human health.Therefore,we studied the toxicity of cadmium on microglia and mechanisms in it.To study the toxicity of cadmium to microglia,cell viability,apoptosis,migration,phagocytosis,expression of inflammatory cytokines and autophagy of BV2 microglia were detected in this study.MTT assay was used to detect the cell viability of microglia.Cell apoptosis was detected by flow cytometry and fluorescence microscopy.We found that cadmium chloride reduce the viability of BV2 microglia and lead to cell apoptosis significantly.To further study the effect of cadmium on the cell function of BV2 microglia,cell scratch test was used to detect the migration of BV2 microglia,fluorescence microscopy was used to study the phagocytosis of BV2 microglia,and q-PCR was used to detect the expression of inflammatory cytokines in BV2 microglia.We found a decrease of migration and phagocytosis of BV2 microglia when exposing to cadmium.Cadmium also reduced the ability of cytokines such as TNF-α,IL-10 and i NOS secretion in BV2 microglia when activated by LPS.To study the mechanism of cadmium’s toxic effect on BV2 microglia,western blotting was used to detect the expression level of autophagy associated protein LC3Ⅱ.We found cadmium reduced the expression of LC3Ⅱ.To further demonstrate that cadmium triggered cell apoptosis by autophagy pathway,rapamycin was used to active autophagy in BV2 microglia.Results showed that rapamycin significantly inhibited BV2 microglia apoptosis induced by cadmium.In all,we found that cadmium induced apoptosis and caused damage in cell function of BV2 microglia.Cadmium also reduced the level of autophagy in BV2 microglia.By elevating the level of autophagy in BV2 microglia,apoptosis induced by cadmium was reduced.This research provides a new idea for the treatment of heavy metal poisoning.