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The Expression Of Transforming Growth Factorβ1,CollegeⅣ,Decorin And α-smooth Muscle Actin (SMA) In Kidney Of STZ Induced Rats

Posted on:2004-03-15Degree:MasterType:Thesis
Country:ChinaCandidate:X X ZhaoFull Text:PDF
GTID:2144360092990663Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
. STUDY BACKGROUND AND OBJECTION:Diabetic nephropathy is one of the most important microvascular complications of diabetes and it attributes to increasing mortality rate of diabetes. The primarypathological alterations of early diabetic nephroathy include renal hypertrophy, thickening of glomerular basement membrane, processing mesangial expansion,. The primary pathological alterations of terminal diabetic nephropathy are glomerulosclerosis and interstitial fibrosis. transforming growth factor PI (TGF PI) has been focused on as a main factor in regulating glomerulosclerosis and interstitial fibrosis because it is interrelated with many metabolic abnormity of diabetes and it directly accelerates ECM synthesis and restrains degration of Type IV collagen through regulatory effects on degrading enzymes. Type N collagen is the main component of glomerular basement membrane and ECM and its abnormal expansion will cause glomerulosclerosis and interstitial fibrosis, the typical aterations of diabetic nephropathy. So far there is no specially good therapy in diabetic nephropathy, but the therapy through blocking the activity of TGFP 1 is now studied by many scientists. Decorin is a natural glycoprotein and antagonist of TGFP 1. The expression and function of Decorin in diabetic nephropathy are still unclear, a -SMA is a kind of cytoskeletal protein and the unique indicator of myofibroblast. Few a -SMA are expressed in normal renal cortex except in vascular media. In early diabetic nephropathy, the proliferational or activated mesangial cells can express a -SMA. Detecting the expression of TFG 1, Decorin college and a-SMA protein in the kidneys of streptozotocin(STZ) induced rats will provide theoretic foundation for therapeutic strategy. METHODS:Male Sprague-Dawley rats(n=87), weighing 180-200g, were grouped randomly for control groups(n-38) and diabetic groups(n=49). Diabetes were induced by intraperitoneal injection of streptozotozin (70mg/kg body wt) after 12h fasting, the levels of blood glucose and urine glucose were determined 48h and 72h after the injection. The rats with blood glucose levels above 16. 8mmol/L(300mg/dL) and urine glucose levels above +++ were considered as diabetic rats. Six Rats of each diabetic group and control group were executed on the 3days, 7days, Hdays, SOdays, 60days and 90days after diabetic rat models were established. Collecting their urine, arterial blood and kidneys. The levels of blood glucose, serum creatinine, serum BUN, urinary creatinine were measured by autobiochemiassay. The kidneys were weighed and the left kidneys were dipped into formaldehyde solution immediately and made to be paraffin slices and immunohistochemistry were done. Immunostaining was semiquantitated at 400 X magnification by using an imageanalysis software, the average score of 15 randomly selected glomeruli was calculated. Results were expressed as mean + Se and statistic analysis is processed in SPSS 10.0,P<0. 05 is regarded as significant.RESULTS:1. The renal hypertrophy indexes of each diabetic groups were significantly greater than those of control groups, statistic difference occurred since 3days (P<0. 05) . Blood BUN of each diabetic groups were significantly higher than those of control groups at every observed timepiont(P<0. 05). Also was blood creatinine concentration except there was no statistic difference at 90days. Creatinine clearance rate of each diabetic groups were significantly lower than those of control groups, statistic difference occurred since 3days (P<0. 05) .Urinary albumin excretion of each diabetic groups were significantly greater than those of control groups, statistic difference occurred since 3days (P<0. 05) .2. The expression of TGFP 1, decorin and college IV proteins of diabetic groups were gradually increased in the glomerulus with time prolonged, the peak is at 60days. There were no statistic differences in the expression of TGFP 1, decorin and college IV proteins in control group among the different observed timepionts. The expression...
Keywords/Search Tags:diabetic nephropathy, diabetic rats, transforming growth factor β 1, college Ⅳ, Decorin, α-smooth muscle actin
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