The Therapeutic Target Of MTOR In1.25-dihydroxyvitamin D3Regulating Thy-1Nephritis Rats And Its Mechanism

Purpose The aim of this study is to investigate the correlation between mTOR and the procedure of1.25-dihydroxyvitamin D3(1.25(OH)2D3) regulating Thy-1rat nephritis model, and the target of1.25(OH)2D3.Methods60healthy male SD rats were randomly divided into four groups: control group(CG), nephritisgroup(NG), Nephritis+1.25(OH)2D3Group (NVG), and Nephritis+1.25(OH)2D3+Rapamycin Group(NVRG)，each group contained15rats. All the rats except CG group were single injected anti-Thy1monoclonal antibody via tail intravenous at a dose of25μL/100g to induce mesangial proliferationglomerulonephritis model. After the nephritis rats were successfully established, the rats in NVG andNVRG group were intervened by1.25(OH)2D30.5μg/(rat·d) and the rats in NVRG group were intervenedby rapamycin1mg/（Kg·d）until the21st day.3rats randomly selected from each group were killed by day1,3,7,14and21after intervention. The samples of24-hour urine were collected by day before killed todetect24-hour urinary protein excretion. The renal tissue samples were separately stained with hematoxylin&eosin and PAS to determine the renal pathological variation, and detected the expression of mTOR,PCNA by immunohistochemistry.Results1.Massive urinary protein was induced in NG group by day1after injection of anti-Thy1monoclonal antibody, reached peak by day3, and returned to normal by day21. The urinary protein levelsat different time points were lower in NVG and NVRG group than those in NG group（p<0.05）, andreturned to normal by day14.2. The renal tissue samples appeared pathologic changes by day3afterinjection of anti-Thy1monoclonal antibody, peaked by day7, and returned to normal by day21. Thepathologic lesions levels at different time points were lower in NVG and NVRG group than those in NGgroup（p<0.05）, and there was no significant differences between two groups.3. Compared with CG group,the expression of PCNA and mTOR were increased significantly in NG group（p<0.05）; Compared withNG group, the expression of PCNA and mTOR were reduced significantly in NVG and NVRG group（p<0.05）; There was no significant differences in expression of PCNA and mTOR between NVG andNVRG groups（p＞0.05）.Conclusion1.1.25(OH)2D3can significantly inhibit the proliferation of mesangial cells in rats.2.mTOR take part in the procedure of1.25(OH)2D3regulating Thy-1rat nephritis model, and maybe thetarget of1.25(OH)2D3.