Effects And Mechanisms Of Nano-Cu Subchronic Exposed On The Spleen Of Rats

Many researches indicated that nano-copper?Nano-Cu?can cause damage on spleen and immune system,while the mechanisms are poorly understood.Therefore,the toxicitys of 80-100 nm Nano-Cu caused on the spleen of rats were researched,and the experiment of dose-dependence of Nano-Cu on spleen immune injury conducted.The subchronic toxicity model of rats was established through exposed 80-100 nm Nano-Cu by intragastric administrations during the 28 days.From the organ coefficient,lymphocyte subsets,immunoglobulin and histopathology to research the effects of Nano-Cu exposed on splenic tissue and immune function.From oxidation/nitridation factors,inflammatory cytokines and signal pathways to research the preliminary mechanism of spleen injury caused by Nano-Cu exposure.All work that we have done to provide the important experimental data relevant to the effects of splenic tissue and immune injury exposed to Nano-Cu by intragastric administrations with 50,100,and 200 mg/kg body weigh for 28 consecutive days.The main results include:1.To research the toxicity of Nano-Cu,the subchronic toxicity model of rats was established by intragastric administrations during the 28 days.The results show that in the Nano-Cu low-,medium-and high-groups,the accumulation of copper signifcantly increase,in a dose dependent manner;in the Nano-Cu medium-and high-groups,the weights of rats increase,while the weight of rats and index of spleens decrease,in a dose dependent manner;in the Nano-Cu medium-and high-groups,Nao-Cu have effect on the RBC,WBC,HCT,Lymphocytes and PLT,whie all of them within the normal physiological range,in a dose dependent manner;the number of macrophages increase in the Nano-Cu low-,medium-and high-groups,besides homogeneous and light-stained amyloid deposits are observed in the high group;in summary,Nano-Cu causes damage on the spleic tissue of rats.The concentration of CD3⁺,CD3⁺CD4⁺,CD3⁺CD8⁺,B and NK cells,as well as IgA,IgG and IgM,decrease in the Nano-Cu medium-and high-groups,in a dose dependent manner;in summary,Nano-Cu causes damage on the spleic and immune system of rats by subchronic exposure.To sum up,Nano-Cu causes damage on the spleen tissue and immune system of rats by subchronic exposure.2.To research the preliminary mechanism of spleen injury caused by Nano-Cu,the subchronic toxicity model of rats was established by intragastric administrations during the28 days.The results show that in the Nano-Cu medium-and high-groups,the expression of oxidants?iNOS?NO?MDA?and anti-oxidants?GSH-Px?CAT?SOD?increase,in a dose dependent manner;spleen is into an oxidative stress state.The gene transcription and protein espression of NF-?B,TNF-?,IFN-?,MCP-1,MIF,MIP-1?,IL-1?/-2/-4/-6 and Bax increase in the Nano-Cu medium-and high-groups,while Bcl-2 decrease,in a dose dependent manner;spleen is into inflammation and apoptotic state.In the Nrf2 signal pathway,the gene transcription and protein espression of Bach1,Nrf2 and HO-1 increase in the Nano-Cu medium-and high-groups,while Bcl-2 decrease,in a dose dependent manner;Nrf2 signal pathway play a protective effect on spleen.In the MAPKs and PI3K/Akt signal pathways,the gene transcription and protein espression of JNK,p38,ERK_1/2,PI3-K,Akt,CREB,AP-1 and COX-2 increase in the Nano-Cu medium-and high-groups,in a dose dependent manner;MAPKs and PI3K/Akt signal pathways make spleen is in an inflammatory state and regulate immune system by regulating the synthesis of PGs.To sum up,Nano-Cu causes damage on the spleen tissue and immune system of rats may by oxidantive strass,inflammatory and apoptosis.In summary,Nano-Cu could accumulate in the spleen of rats,in a dose-dependent between.Nano-Cu exposed on rats by intragastric administrations for 28 consecutive days had bad influence on the tissue and immune system of spleen;Nano-Cu exposed on rats by intragastric administrations for 28 consecutive days could significantly increase the levels of stress factors,as well as Nrf2 singnal pathway;Nano-Cu exposed on rats by intragastric administrations for 28 consecutive days mediated the inflammation and programmed cell death response by up-regulation the gene transcription and protein expression levels of NF-kB?inflammation?and COX-2?MAPKs,PI3-K/Akt signal pathway?,resulting in the damage of tissue and immune system of spleen on rats.