The Role Of Endoplasmic Reticulum Stress In Mouse Glomerular Podocyte Apoptosis Induced By Contrast Medium And The Protection From Atorvastatin

[Objective] TO investigate the change and effect on the endoplasmic reticulum stress inmiceglomerular podocyte apoptosis induced by Contrast medium and the protection from Atorvastatin.[Methods]As the research object,under the serum-free and hypoxia condition,Glomerular podocytes in mice were cultivated and exposed to concentration 0,40,60,80,120,150,200 mg I/ml of iohexol for 2 h in Cell culture box(33℃、0.5%CO2),and exposed to iohexol(120 mg I/ml)for0,1,2,4,6,8,10,12 h,respectively,under the serum-free and hypoxia condition,In the separate experiments,cells were incubated with different concentrations of ATO(10-10,10-9,10-8,10-7,10-6,10-5 mmol/L)for 24 h,and then exposed to iohexol(120 mg I/ml)for 2 h under serum-free and hypoxia.Cell proliferation capability was detected by MTT assay.Cell apoptosis was detected by TUNEL.The relative m RNA expression of GRP-78 、 Chop 、 capase12 、 bax and bcl-2 were analyzed by reverse-transcription polymerase chain reaction(RT-PCR).The relative protein expression of GRP-78 、 Chop 、 capase12 were analyzed by Western-blotting.[Result] MTT assay showed that,compared wtih normal group,the proliferation of cells were inhibited in different degrees in the group of diffrerent concetration of iohexol,significantly inhibited in the group of 120,150,200 mg I/ml.At the same concentration of iodine alcohol intervention,proliferation of cells was significantly depressed in different time intervention group.At the same concentration of iodine sea alcohol,under the condition of the same incubation time,after atorvastatin treatment,cell proliferation ability was enhanced,significantly enhanced in the concetration of 10-6mmol/L.Tunnel assay showed that,compared wtih normal group,cell apoptosis was most significant in the group of CM and HSF+CM,especially in the group of HSF+CM,and ATO could decrease cell apoptosis.PT-PCR assay showed that,the expression of the m RNA of GRP-78、Chop、capase12、bax could be up-regulated by CM,and the expression of the m RNA of bcl-2 could be down-regulated by CM.However,ATO can dereased the expression of m RNA of GRP-78、Chop、capase12 and bax,but increased the expression of the m RNA of bcl-2.Western Blot assay showed that CM could promote the protein expression of GRP-78、Chop and capase12.However,ATO can up-regulate the protein expression of GRP-78、Chop、capase12.[Conclusion] Under the condition of ischemia and hypoxia,the contrast agent could induce the apoptosis of mouse glomerular podocytes in a time and concentration dependent manner.The contrast agent induced apoptosis of mouse glomerular podocytes may be related to ERS.Vasatin has protective effects on contrast agent-induced apoptosis of mouse glomerular podocytes,which may be related to the level of inhibition of endoplasmic reticulum stress.