中文摘要：

目的通过观察塞来昔布（CXB）对常染色体显性多囊肾病（ADPKD）动物模型Han：SPRD大鼠的作用，从而研究CXB延缓肾衰竭进展的机制。方法选取3周龄杂合（cy／＋）Han：SPRD大鼠共57只，随机分成3组（每组19只）进行实验。按照CXB在饲料中的含量分为对照组（0mg·kg^-1·d^-1）、小剂量组（3mg·kg^-1·d^-1）和大剂量组（10mg·kg^-1·d^-1）。在大鼠4、6、8、10、12和16周龄时测定血清BUN、Scr。ELISA法检测16周龄大鼠血浆6-酮前列腺素F1α（6-keto—PGF-1α）和血栓烷B2（TXB2）的含量。实时荧光定量PCR法检测大鼠肾组织肿瘤坏死因子α（TNF—α）的mRNA水平。免疫荧光共聚焦显微镜检测TNF—α和环氧化酶2（COX-2）的蛋白表达。Western印迹检测16周龄大鼠TNF—α的蛋白表达量。结果对照组BUN、Scr持续升高，分别于6、8周龄时即大于正常范围；至16周龄时，BUN为（26．56±9．19）mmol／L，Scr为（95．08±67．54）μmol／L；CXB小剂量组和大剂量组均能减缓BUN、Scr上升速度，减小其上升幅度。16周龄大鼠CXB小剂量组血浆中6-keto—PGF-α和TXB2[（1831．68±233．31）ng／L和（156．62±9．29）ng／L1和大剂量组两者的含量[（1148．57±105.80）ng／L和（157．87±10．16）ng／L]均显著低于对照组[（2792．26±830．48）ng／L和（248．88±93．72）ng／L]（均P〈0．05）。实时荧光定量PCR结果示，16周龄大鼠肾组织小剂量组和大剂量组TNF—α mRNA水平均显著低于对照组（均P〈0．05）。免疫荧光共聚焦显微镜显示，对照组TNF-α和COX-2在小管间质区高表达，小剂量组和大剂量组荧光强度显著减弱。与对照组比较，CXB小剂量组和大剂量组大鼠肾组织蛋白表达量显著减少，差异有统计学意义（均P〈0．05）。结论CXB可能通过抑制COX-2的活性，阻止膜磷脂释放花生四烯酸代谢产物6-keto—PGF-1α和TXB2，减少炎性因子TNF-α的含量，正?

英文摘要：

Objective To investigate the amelioration mechanism of renal dysfunction by Celeeoxib （CXB） through the observation of CXB on Han： SPRD rats with ADPKD. Methods Fifty-seven 3-week-old male Han：SPRD heterozygous （Cy/＋） rats were randomly divided into 3 groups （n=19）. One group was fed with normal forage （control group）, another two groups were fed with low dosage （3 mg·kg^-1·d^-1） and high dosage （10 mg·kg^-1·d^-1） administration of CXB respectively. The BUN and Scr were determined respectively at 3, 5, 7, 9, 12 and 16 weeks. The content of 6-keto-PGF-1α and TXB2 was measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TNF-α mRNA was detected by real-time RT-PCR assay. The coexpression of TNF-α and COX-2 was examined by double immunofluorescence labeling technique and laser scanning confocal microscopy. The expression of TNF-α protein was detected by Western blotting. Results BUN and Scr increased continuously in control group and exceeded the normal at 6-week-old and at 8-week-old respectively. At 16-week-old, BUN and Scr were （26.56±9.19） mmol/L and （95.08±67.54）μmol/L. After being treated with CXB, the progression of BUN and Scr was reduced in both low and high dosage group. The content of 6-keto-PGF-1α and TXB2 in low [（1831.68±233.31） ng/L and （156.62±9,29） ng/L] and high dosage group [（1148.57±105.80） ng/L and （157.87±10.16）ng/L] was significantly lower than those in control group [（2792.26±830.48） ng/L and （248.88±93.72） ng/L]. TNF-α mRNA levels in low[（2.52±0.01）×10^3} and high dosage group[（2.48±0.02）×10^3] were both decreased as compared to control group[（6.17±0.19）×10^3]. The co-expression of TNF-α and COX-2 distributed widely in tubulointerstitial area in control group and only few in low dosage group. More TNF-α protein in CXB-treated group was detected than that in control group. Conclusion CXB can slow down disease progression in Han： SPRD rats with renal dysfunction through