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The Changes And Relationship Of Decorin And TGF-β1 MRNA In Renal Cortex Of Diabetic Rats

Posted on:2004-05-10Degree:MasterType:Thesis
Country:ChinaCandidate:J H ZhangFull Text:PDF
GTID:2144360092490788Subject:Medicine
Abstract/Summary:PDF Full Text Request
Objective: Diabetic nephropathy (DN) is one of the most important chronic complications of diabetic mellitus. It severely influences the life qualities of patients. It is also a heavy economic burden to patients, their families, and the society. TGF- (transforming growth factor- ) is commonly regarded as one essential factor of inducing kidney f ibrosis. And it may be the last public step of fibrosis progress. Some reseachers have succeeded in using antibody or antisense nucleotide of TGF- to retard the kidney fibrosis when they did not change the high glucose condition. But it is not a convenient method to apply heterogeneity protein on the patients for a long time. It has been found that the core proteins of some proteoglycans, such as betaglycan and decorin, could combine with TGF- , and inhibit the activity of TGF- . These proteoglycans are self component of tissue. Decorin is mostly in the connective tissue which is enriched of I-type and II-type collagens. It not only combines with TGF- , but also modulates the cell proliferation, differentiation, ECM formation, collagen structure, et al. Then it has a very close relationship with fibrosis. There are some support evidences of using decorin to cure inflammation kidney diseases. Whereas little has been know about the possibility and effects of using decorin to treatnon-inflamination kidney fibrosis, such as diabetic nephropathy. And we also not very clearly learn the changes and relationship of decorin and TGF- 1 in diabetic nephropathy with considering the disease course influence. In this study, we investigate the changes and relationship of decorin mRNA and TGF- P , mRNA in renal cortex of streptozotocin induced diabetic rats and evaluate the effects of decorin and TGF- 1 on the development of diabetic nephropathy.Methods: 87 male SD rats were randomly devided into control group (n=38) and diabetic group (n=49). 6 rats were randomly sacrificed in each group at different observed time (at the 3rd 7th 14th 30lh 60th 90th days after succeeding in being diabetes). The rest rats were raised for avoiding accident death or failure in being diabetes. Diabetes was induced by a signal injection of streptozotocin (STZ, 70mg/kg) into the left lower abdominal cavity. Decorin mRNA and TGF- 1 mRNA values in renal cortex were determinded by RT-PCR(referred to P -actin mRNA values). Body weights, kidney weights, the levels of urine (blood) glucose, urine (blood) creatinine (Cr), BUN and urine albumin were also measured. And the creatinine clearance rate (CCr), the kidney hypertrophy index and urinary albumin/Cr value were calculated at every observed time point. Using SPSS10. 0 software to analyze the data.Results:After injection of STZ, 92%(45/49) rats of diabetic group had achieved the determining level. 9 of 45 diabetic rats (20%) and 1 of 38 control rats (2.6%) died accidently during the experiment.Diabetic rats showed obvious clinical symptoms. At any observed time point, the body weights of diabetic rats were smaller than those of normal rats, but the kidney hypertrophy indexes were larger than those of controlgroup (P<0. 05 or P<0.01). Diabetic group had higher levels of blood Cr (P<0. 05 or P<0. 01, except the 90tk day) and BUN (P<0. 05 or P<0. 01) and lower levels of creatinine clearance rate (CCr) (P<0.05 or P<0. 01, except the 7th day). The urinary albumin/Cr values of diabetic group were much greater than those of normal rats at every observed time point (P<0. 05 or P<0.01).Decorin mRNA levels in the renal cortex of control group varied delicately and there were no statistic differences among the 6 observed time points(p>0.05). Comparing to the normal rats, diabetic rats had no specific changes at the 3rd 7th 14th days (P>0. 05), but began to slightly increase at the 30th day (P>0. 05 ) , and achieved the top value at the 60th day(P<0. 05), then decreased a little at the 90th day(P=0.01). The decorin mRNA values of diabetic group at the 6 observed time points had a significant statistical difference (P<0.01).The alt...
Keywords/Search Tags:ProteoglycanⅡ(decorin, PGⅡ), TGF-β1(transforming growth factor-β1), Diabetic nephropathy
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