| [Background and Objective Chronic interstitial nephritis is the second kind of kidney disease that is only next to glomerulopathy, if conditions can not be controled , eventually tubulointerstitial fibrosis will appear. In the patients of end-stage ranal stage, about 15%-25% are caused by tubulointerstitial fibrosis. Obstructive nephropathy is the common reason in the clinical diseases of renal stroma damage. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second kind of medicine that is only next to anti-infective all over the world, but it's side effects have restricted it's application, especially to the patients taking medicine of big dosage for a long period. During the work of seeking NSAIDs with higher curative effect and less side effect, two inferior types of COX had been discovered. Cyc100xygenase(COX) is the key limited enzyme in the metabolism process of prostaglandin, About ten years ago, two COX isoforms(COX-l and-2) were demonstrated: COX-1 expresses stably and COX-2 is expressed by a number of inflammatory stimuli. COX-1 products are involved in regulating physiological functions to maintein the stability of milieu interieur whereas COX-2 products play a pathologic role in many tissues and organs ( such as inflammatory reactions, tumor,et). The discovery of COX-2 make people recognize the physiological and pathologic role of COX again, this indicates the therapy results of NSAIDs can separate from it's side effects. Many selective inhibitors of COX-2 are now available, they are often used to cure rheumatic arthritis ,ostearthritis and other diseases. However domestic and international researches of selective or specific COX-2 inhibitor about the influences on various kidney disease are scarce, especially the reportes about the correlation of COX-2 and tubulo interstitial fibrosis. Unilateral ureteral obstruction(UUO) is the frequently used method to induce the damage of the renal stroma. It is confirmed that a lot of inflammatory cells infiltrate to tubulointerstitium. The expression of many factors are higher than usual, such as TGF-B1.IL-1, IL-6, FGF, TNF, PDGF, NO. These factors have important role in the occurrence and development of UUO. COX-2 also take part in this pathologic process because many tests confirm that the expression of COX-2 are significant higher in UUO. Domestic and international researches all indicate that selective COX-2 inhibitors can alleviate tubulointerstitial fibrosis of UUO rats. Selective COX-2 inhibitor might exert its salutary effects through down-regulation of TGF-B1. Some scholars reported that the overexpression of COX-2 in the renal cortex of UUO perhaps is the reason of the infiltration and accumulation of inflammatory cells. There are a lot of factors can improve the expression of COX-2 in the pathologic process of tubulointerstitial fibrosis induced by UUO. It is well known that traditional NSAIDs have many bad side effects. One of them is Chronic interstitial nephritis. It might correlate with the blockade of COX-1. In conclusion. Theoretically blocking COX-2 selectively to retify disease does not affect the physiological state of organism at the same time avoid the side effects of traditional nonsteroidal anti-inflammatory drugs. In the present study COX-2, NO and TGF-B1 in the kidney tissue were measured at the 2th week to investigate their effects in the pathogenesis of UUO. Meanwhile rofecoxib was used in the UUO rat model to explore the mechanisms of its renal protective effects on UUO by observing its influence on COX-2, NO and TGF-B1.[ Methods ] 24 Wistar rats were randomly assigned to following groups: sham-operation group(C) unilateral ureteral obstruction(UUO) group(U) rofecoxib treatment group(R). Each group has 8 rats. A day before operation and after operation, R were treated with rofecoxib(10mg/kg/d) . whereas C and U with same volume N.S. At the 2th week after operation, biochemistry tests of b100d and urine were performedto measure the quantity of 24h urinary protein and the concentration of urinary TXB2. Kidneys were...
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