Renal Protection Of Mobic In Type Two Diabetic Rats And Its Mechanisms

Object To develop a rat model of type 2 diabetes.To observe the renal express of cyclooxygenase-2 (COX-2) in rats with 2 diabetes and selective COX-2 inhibitor-Mobic on renal expression of COX-2,matrix metalloproteinase-9(MMP-9) , tissue inhibitor of matrix metalloproteinase-1(TIMP-1) and urinary TXB2, 6-Ket-PGF1 a excretion.Further explore the effect of Mobic on renal struction ,function, urinary protein and its mechanism.Methods Eighteen Sprague-Dawley rats (male,180-200g body weight) were divided into four groups of normal rats, diabetic rats, diabetic rats treated with mobic 2mg/(kg d).After 6 weeks, Immunohistochemistry was used to measure the protein level of COX-2,MMP-9,TIMP-1 and the urinary thromboxane B2 , 6-Ket-PGF1 a concentration was determines by radioimmunoassay. In addition, the renal tissue were observed by light microscopy.Results (1) Insulin resistance was induced by feeding dies enriched in sucrose and fat,and hyperglycemia was induced with a dose of STZ that did not cause diabetes in chow-ed rets. After 6 weeks,rats of model group presented itself early changes of diabetic nephropathy. (2) The renal expression of COX-2 and TIMP-1 was significantly higher in the type 2 diabetic group than in the normal group,but the expression of MMP-9 was on the contrary(p<0.05);At the end 6th6 week,the excretion of urinary TXB2, 6-Ket-PGF1 was higher in the diabetic group than in the normal(p<0.05). (3) In the mobic-treated group,the intensity of renal expression of COX-2,TIMP-1,MMP-9 and the urinary excretion of TXB2, 6-Ket-PGF1 24-hour urine protein was bewteen the normal group and the diabetic group(p<0.05);The index of matrixes density was lower in the mobic-treated group than in the diabetic group ,although higher than in the normal group(p<0.05).Conclusion (1) A rat model of type 2 diabetes mellitus is developed successfully by combination of dietary-induced insulin resistance and low-dose STZ-induced hyperglycemia. (2) COX-2 is involved in the pathogenesis of the injury oftype 2 diabetic nephropathy. (3) Selective COX-2 inhibitor mobic might exert its salutary effects through several aspects, including preferential blockade of COX-2 expression, inhibiting postglandings systhesis and modulated MMP-9, TIMP-1 expression.