| PrefaceInflammation and fibrosis of renal tubular interstitial are closely attached to the development of renal diseases , prevention or delay of which has become the hot point of research in the field of kidney disease currently . Unilateral ureteral obstruction ( UUO) is relatively a mature model for renal interstitial fibrosis, and its morphology characteristic is the accumulation of matrix proteins and the proliferation of the fibroblasts , which results from multifold aspects . As we know ,the tow important factors which lead to mononuclear macrophage infiltration during the early stage of UUO is the increased expression of chemoattractant factors and adhesion factors . Their promoter include the compounding site of nuclear factor kappaB (NF - KB ). Correspondingly, the activation of NF - KB regulates their transcription and expression, and indicates that increase of its activation may involve in the pathogenesis of the injury of UUO . Recently research confirms that specific cyclooxygenase - 2 inhibitor compared with NSAIDs, can decreased renal interstitial fibrosis of UUO rats without clearly mechanism . In this study , we develop a rat model of UUO and to investigate the effect of rofecoxib on activation of renal NF - KB and MCP - 1 in this model.Materials and methods1. Experimental animalsMale Wistar rats(n =24) ,weighing 180g -220g , aged 7-9 weeks, were randomized to four groups : 1) model rats untreated , n = 6; 2) rofecoxib treated rats , n = 6 ; 3) indomethacin treated rats ; n = 6 ; 4) normal controls , n = 6 ( sham operated group ) . After adaptive observation one week , the eight-een rats in 1) , 2) and 3 ) were left ureteral ligature , the rats in control group were sham operated . Peroperation of 24 hours , the rats in group 2) were administered orally by rofecoxib 10mg/kg/d , the rats in group 3 ) were giving in-domethacin (4 weeks ) , giving normal saline of the equal volume to the rats in group 1 ) and group 4 ) . At the 4th weekend , we collect the 24 - hour urine of the rats from each group which were placed individually in metabolic cages . The rats were put to death then kidneys and arterial blood were obtained .2. Indices assayed2. 1 Serum creatinine and blood urea nitrogen were detected with automatic biochemical analyzer.2. 2 The urinary thromboxane B2 concentration was determined by radioim-munoassay.2. 3 Kidney morphology : routine HE , PAS and Masson staining.2. 4 The protein level of NF - KB , MCP - 1 , TGF - B1 and Col IV were measured by irnmunohistochemistry .3. Statistical analysisResults were expressed as mean + SD ( x + s). Comparisions among 4 groups were analyzed by one - way analysis of variance , followed by LSD multiple comparision test to evaluate statistical difference between 2 groups , p <0. 05 is considered as significant .Results1. Blood creatinine and urea nitrogenBlood creatinine and urea nitrogen levels of group 1 ) were significantly higher than that of group 4 ) (P < 0. 05). After treatment of roficoxib, blood creatinine and urea nitrogen decreased , while the levels of group 3 ) were similar to those of group 1 ) .2. the urinary thromboxane B2The urinary thromboxane B2 concentration in group 1 ) increased substantially than that of group 4 ) ( P < 0. 05 ). Both roficoxib and indomethacin reduced it , while the effect of roficoxib was greater( P <0.01).3. Kidney morphologyNo clearly pathology was seen in group 4 ) . In group 1 ) , degeneration and necrosis of tubular epithelium occurred , as well as atrophy or dilation of the renal tubules . And we can see expanded extracellular matrix , increased of col-lagens , intersititial fibrosis with inflammatory cells infiltration . In group 2 ) , roficoxib improves the above - mentioned histological changes. While there were no obviously distinction between group 3 ) and group 1 ) .4. Expression of NF - KB ,MCP - 1 , TGF - B1 and IV of type collage in kidneyIn group 1 ) ,the expression of NF - KB , MCP - 1 , TGF - B1, and Col IV in kidn...
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