ABSTRACT
Abstract Purpose: To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN). Methods: The Sprague Dawley rats were divided into normal control (NC) group (n = 12), DN group (n = 11), and DN+RAM group (n = 12). The ratio of renal weight to body weight (RBT), fasting blood glucose (FBG), HbA1c, 24-h urine protein (TPU), blood urea nitrogen (BUN), creatinine (Cr), renal pathological changes, the levels of IGF-1, fibronectin (FN), type IV collagen (Col-IV), and matrix metalloproteinases (MMP)-2 were compared among the groups. Results: Compared with NC group, the RBT, FBG, HbA1c, TPU, BUN, Cr, and RMM in DN group were significantly increased (P < 0.05), the IGF-1, FN, and Col-IV were significantly upregulated (P < 0.05), while MMP was significantly downregulated (P < 0.05). Compared with DN group, the indexes except for the FBG and HbA1c in DN+RAM group were significantly improved (P < 0.05), among which IGF-1 exhibited significant positive correlation with TPU(r=0.937), FN(r=0.896) and Col-IV(r=0.871), while significant negative correlation with MMP-2 (r=-0.826) (P<0.05). Conclusion: RAM may protect the kidneys by suppressing IGF-1 and mitigating the accumulation of RMM.
Subject(s)
Animals , Male , Rats , Insulin-Like Growth Factor I/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Ramipril/pharmacology , Diabetic Nephropathies/drug therapy , Mesangial Cells/drug effects , Insulin-Like Growth Factor I/metabolism , Immunohistochemistry , Fibronectins/drug effects , Fibronectins/metabolism , Rats, Sprague-Dawley , Matrix Metalloproteinases/drug effects , Matrix Metalloproteinases/metabolism , Collagen Type IV/adverse effects , Collagen Type IV/metabolism , Diabetic Nephropathies/metabolism , Mesangial Cells/metabolismABSTRACT
Los glucocorticoides son usados comúnmente para el tratamiento de enfermedades inflamatorias, autoinmunes, enfermedades malignas, y en la prevención de rechazo de órganos trasplantados. Un efecto secundario frecuente del tratamiento prolongado es la pérdida de masa ósea que se produce por varios mecanismos y es causa de osteoporosis y fracturas vertebrales. El tratamiento con disfosfonatos ha sido propuesto para esta situación. Presentamos un caso clínico de osteoporosis grave en una niña con dermatomiositis juvenil, que respondió favorablemente al tratamiento con disfosfonatos orales.
Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor) and IGFBPs (binding IGF I proteins necessary for bone metabolism), and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.