Effects Of Low Dose Copper Exposure On Liver Function And Expression Of Inflammatory Cytokines In Rats And Intervention Of Lactic Acid Bacteria

Objective:1.To observe the effects of low dose of copper exposure on liver function and expression of inflammatory cytokines in rats;2.To investigate whether lactic acid bacteria(LAB)can influence hepatic function and expression of inflammatory cytokines in rats exposed to copper.Methods:Wistar rats were randomly divided into 8 groups: high copper group,medium copper group,low copper group,high copper + LAB group,medium copper + LAB group,low copper + LAB group,LAB group and blank control group.Rats were intervened for 30 days.1.At the end of the experiment,isolated the rat blood,liver,spleen and thymus,and calculated the indices of liver,spleen and thymus.2.Pathological changes of liver in rats were performed by H&E staining,and observed under microscope.3.Rat liver function markers,including alanine aminotransferase,aspartate aminotransferase and albumin,were measured in rat serum.4.Copper content in rat serum was measured by ICP-MS.5.Liver oxidation indices including superoxide dismutase,malondialdehyde and glutathione peroxidase were measured by rat liver tissue.6.IL-1,IL-6,IL-10,IL-12,SOD and TNF-? m RNA in liver were detected by RT-PCR.Results:1.Indices of liver,spleen and thymus were of no significant difference in every group(P>0.05).2.Pathological examination showed that liver of rats exposured to copper,especially high copper,were damaged.When LAB was given to rats,the liver damages were abolished.3.Compared to control group,ALT and AST significantly increased and ALB significantly decreased in three different doses of copper group(P<0.05);under the intervention of LAB,ALT?AST decreased in medium copper group and low copper group and ALB increased significantly compared to copper only groups(P<0.05).4.Compared to control group,the levels of serum copper were significantly increased in high copper group,medium copper group and low copper group(P <0.05);under the intervention of LAB,serum copper increased,but the differences were not significant(P> 0.05).5.Compared to control group,MDA were significantly different in high copper group,medium copper group and low copper group(P<0.05)SOD enzyme activity and m RNA level increased in high copper group and medium copper group;under the intervention of LAB,SOD increased and MDA decreased obviously compared to high copper group and medium copper group(P<0.05).6.Compared to control group,the levels of IL-1?,IL-6,IL-10 and TNF-? m RNA were significantly higher in high copper group,medium copper group and low copper group;while the level of IL-12 m RNA was significantly higher only in high copper group than that of blank control group(P<0.05);under the intervention of LAB,the levels of IL-1,IL-6 and TNF-? m RNA decreased obviously compared to copper only groups(P<0.05).Conclusion:1.Different doses of copper exposure can cause significant changes of AST,ALT and ALB,suggesting that copper exposure reduced liver function in rats;2.Under the intervention of LAB,the protein level of ALTand AST decreased and ALB increased significantly compared to copper only groups,suggesting that LAB may improve liver function of rats exposured copper;3.Compared to control group,the levels of IL-1?,IL-6,IL-10 m RNA in low copper group were significantly higher,suggesting that low copper exposure caused inflammation in rat liver;4.Under the intervention of LAB,the levels of IL-1?,IL-6 and TNF-? m RNA in low copper group decreased obviously,suggesting that LAB could reduce liver damages caused by copper through reducing the release of inflammatory cytokines.