| 摘要: |
| 目的:观察塞来昔布(celecoxib,CXB)对常染色体显性遗传性多囊肾病（autosomal dominant polycystic kidney disease,ADPKD)模型Han：SPRD大鼠肾囊肿生长的作用，探讨其可能的作用机制。方法:3周龄杂合（cy/+)Han：SPRD大鼠随机分成3组（n=19)：小剂量（3 mg·kg-1·d-1)、大剂量（10 mg·kg-1·d-1)CXB作用组及空白对照组。大鼠饲养至16周龄，称取体质量（TBW)及双肾质量（2K)，计算2K/TBW；取肾组织行H-E染色及特殊染色，观察肾间质炎细胞浸润程度，测定囊肿指数、纤维化指数；采用免疫荧光共聚焦扫描法检测肾组织环氧化酶（COX)-2、增殖细胞核抗原（PCNA)共染的荧光斑表达丰度，采用Western印迹法检测肾组织COX-2、PCNA蛋白表达量。结果:小剂量CXB作用组大鼠2K/TBW低于空白对照组，差异有统计学意义\[（1.10±0.009)% vs (1.33±0.02)%,P＜0.05\]。与空白对照组相比，小剂量、大剂量CXB作用组大鼠肾间质炎细胞浸润程度评分减轻\[（2.6±0.26)、（2.8±0.31) vs （3.7±0.33),P＜0.05\]，肾囊肿指数\[（42.9±6.56)、（47.1±7.28) vs （64.8±6.71)\]、纤维化指数\[（11.2±2.63)、（10.1±3.30) vs （16.3±4.16)\]明显降低（P＜0.05)。小剂量CXB作用组大鼠肾组织COX-2、PCNA共染的荧光斑强度较空白对照组明显减弱，差异具有统计学意义（P＜0.05)；与空白对照组相比，小剂量、大剂量CXB作用组大鼠肾组织COX-2\[（0.326±0.011)、（0.409±0.008)vs （0.814±0.012),P＜0.05\]、PCNA表达量明显降低\[(0.763±0.051)、(0.925±0.042)vs (0.988±0.031),P＜0.05\]。结论:3、10 mg·kg-1·d-1塞来昔布可能通过抑制COX-2活性，减轻炎细胞浸润而发挥抑制Han：SPRD大鼠肾囊肿生长的作用。 |
| 关键词: 塞来昔布 环氧化酶2 常染色体显性多囊肾 囊肿 细胞增殖 |
| DOI：10.3724/SP.J.1008.2009.01140 |
| 投稿时间：2009-04-14修订日期：2009-08-06 |
| 基金项目:国家自然科学基金（30330640，30271523，30570867). |
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| Celecoxib inhibits proliferation of Han: SPRD rat renal cyst through inhibiting COX-2 activity |
| XU Tao1，2,WANG Su-xia1，3,YE Chao-yang1,MEI Chang-lin1* |
| (1.Department of Nephrology,Kidney Disease Research Institute of PLA,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China;2.Department of Nephrology,General Hospital of PLA，Ji’nan Military Area Command,Jinan 250031;3.Department of Hemodialysis,General Hospital of PLA，Ji’nan Military Area Command,Jinan 250031) |
| Abstract: |
| Objective:To investigate the effect of celecoxib (CXB),a specific COX-2 inhibitor,on the proliferation of Han:SPRD-cy rats’ renal cyst,and to probe into the related mechanism.Methods: Totally 57 3-week-old male Han: SPRD heterozygous(cy/+) rats were randomly divided into 3 groups (n=19): control group (fed with normal forage),low dosage CXB group (3 mg·kg-1·d-1) and high dosage CXB (10 mg·kg-1·d-1) treatment groups.The animals and their bilateral kidneys were weighed; the 2-kidney weight/total body weight(2K/TBW)ratio was calculated.The renal cystic index(CI),fibrosis index, and inflammatory cell infiltration in interstitium were observed by pathologic renal tissue slices.The co-expression of PCNA and COX-2 was analyzed by double immunofluorescence labeling technique and laser scanning confocal microscopy.The expression of PCNA and COX-2 protein was examined by Western blotting analysis.Results: The 2K/TBW ratio of the low dosage group(\[1.10±0.009\]%) was significantly lower than that of the control group (\[1.33±0.02\]%) at the 16-week old,(P＜0.05).Compared with the control group,the inflammatory cell infiltration in other two groups was significantly decreased (\[2.6±0.26\],\[2.8±0.31\]vs \[3.7±0.33\]),P＜0.05).The fluorescence intensities of COX-2,PCNA in the low dosage CXB group was significantly lower than those of the control group (P<0.05).Compared with the control group,the other two groups had significantly decreased expression of COX-2(\[0.326±0.011\],\[0.409±0.008\] vs \[0.814±0.012\],P＜0.05) and PCNA (\[0.763±0.051\],\[0.925±0.042\] vs \[0.988±0.031\],P＜0.05).Conclusion: CXB at 3,10 mg·kg-1·d-1 can reduce inflammatory cell infiltration and inhibit the proliferation of Han:SPRD rat’s renal cyst,probably through inhibition of COX-2. |
| Key words: celecoxib cyclooxygenase 2 autosomal dominant polycystic kidney cysts cell proliferation |
