The Expression And Mechanism Of Osteoactivin In SD Rats' Kidney After Acute Cyclosporine A Toxicity

ObjectiveThis study was designed to discuss the expression and mechanism of OA in kidney by establishing the SD rats model of acute cyclosporine A toxicity.MethodsFeed the SD rats with normal diet, a week later,randomly divide them into 3 groups:test group(gavage with cycloporin A and olive oil), vector group (gavage with olive oil) and control group(gavage with physiological saline). SD rats were sacrificed on two days, one week, two weeks afer the gavage, to survey the renal function, the body mass change; Survey the kidney histopathological change with HE staining; Survey the staining degree and area of OA by immunohistochemistry; Survey the OA protein by Western blot;Survey the mRNA expression of the OA,MMP-13,collagen type III by RT-PCR.ResultsThe body weight and SCr of rats in test group on day-2,week-1 have no significant difference compared with vector group and control group(p>0.05),on week-2,weight significantly reduced, SCr significantly increased compared with vector group and control group(p<0.001); The main histopathological changes in test group were inflammatory cell infiltration, vacuolar degeneration of interstitial cell, tubular epithelial cell necrosis. Intense OA expression localized in the tubular epithelium and interstitial fibroblasts in the kidney of test group was detected by immunohistochemistry. After CsA gavage, the relatively expression of OA mRNA,MMP-13 mRNA. Col III mRNA has increased along with the time extending. Western blot analysis showed that, OA protein in the control and the vector control group expressed tracely, the OA protein expression increase along with the extending of time in the test group.ConclusionOA in the SD rats'kidney after acute CsA toxicity has been expressed. It mainly expresses in the tubular epithelia cells and renal interstitium. OA can reflect the damage of kidney tissue caused by CsA more sensitive than SCr.During the period of SD rats renal injure caused by acute CsA toxicity,the early-phase upregulation of OA expres-sion in the tubular epithelium in response to renal injury might play a key role in triggering renal interstitial fibrosis by activation of MMPs expres-sion and collagen remodeling in SD rats.