Leflunomide Diabetic Rats Of Glut-1 Mrna And Tgf-��1 Mrna Expression

Objective To investigate the effects of Leflunomide on the expressions of glucose transporter-1(GLUT-I) mRNA and transforming growth factor-β1(TGF-β1) mRNA in the diabetic rats,and probe its mechanism.Method An animal model of diabetes was established by intraperitoneal injection of STZ.Fifty-four wistar rats were divideded randomly into control group(group A), streptozotocin(STZ)-induced diabetic rat group(group B),Leflunomide treated group(group C).Four rats of each group randomly choosed were sacrificed at the end of the 4^th,the 8^th,the 12^th week,and data of parameters as body weigh,right kidney weight,blood sugar,serum creatinine,blood urea nitrogen,cholesterol,triglyceride and 24-hour urinary protein excretion were collected.Renal GLUT-1 mRNA and TGF-β1 mRNA expression were measured with reverse transcriptase-polymerase chain reaction (RT-PCR).Renal pathomorphology was bserved by HE staining and PAS staining.Laminin and typeⅣcollagen were measured with immunohistochemical techniques.Results 1,(1) Compared with Group A,Blood sugar was increased significantly (p＜0.01) and 24-hour urinary protein excretion did not increased significantly(p＞0.05) at the incipient time when the animal model of diabetes was established successfully in Group B;at the end of 4^th week,body weight was decreased significantly (p＜0.01),while the kidney weight index,serum creatinine,blood urea nitrogen,cholesterol,triglyceride,24-hour urinary protein excretion,renal GLUT-1 mRNA and TGF-β1mRNA expression were increased significantly(p＜0.01) in Group B;compared with Group A,at the end of 12^th week,renal GLUT-1 mRNA and TGF-β1mRNA expression,the kidney weight index and serum creatinine of rats in group C were not incresed significantly(p＞0.05).(2) Compared with Group B,at the end of 8th week,serum creatinine,and blood urea nitrogen were decreased(p＜0.05),cholesterol,24-hour urinary protein excretion and renal GLUT-1 mRNA and TGF-β1mRNA expressions were decreased significantly(p＜0.01) in Group C;at the end of 12^th week,body weight was increased(p＜0.05),the kidney weight index and triglyceride were decreased significantly (p＜0.01) in Group C.(3) the renal GLUT-1 mRNA and TGF-β1mRNA expression were in obvious positive correlation(r=0.975,P＜0.01)2,(1) HE dyeing and PAS dyeing showed that glomcrulus hypertrophia,mesangial cell proliferation,mesangial matrix diffused and nodular multiplication,thicking of the glomerular and tubular basement membrane of rats in Group B.In Group C these changes alleviated.(2) And immunohistochemical(IHC) analysis:the expression of Laminin and typeⅣcollagen were faintly observed in nondiabetic glomeruli,diabetic rats revealed enhanced expression of Laminin and typeⅣcollagen in glomeruli and nephric tubes,Leflunomide -treated diabetic rats revealed decreased expressions of Laminin and typeⅣcollagen in glomeruli and nephric tubes.Conclusion Leflunomide can decrease the 24-hour urinary protein excretion, decreased expressions of Laminin and typeⅣcollagen in glomeruli and nephric tubes of STZ-induced diabetic rats,inhibite the degree of renal hypertrophy and fibrosis hardening. It might be the mechanism that Leflunomide can down-regulate the synthesis of TGF-β1mRNA and then down-regulate the expression and activity of GLUT-1mRNA,and ultimately postpone the development of diabetic nephropathy.