塞来昔布通过抑制COX-2活性抑制Han:SPRD大鼠肾囊肿生长
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国家自然科学基金(30330640,30271523,30570867).


Celecoxib inhibits proliferation of Han: SPRD rat renal cyst through inhibiting COX-2 activity
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Supported by National Natural Science Foundation of China(30330640,30271523,30570867).

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    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。

    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.

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  • 收稿日期:2009-04-14
  • 最后修改日期:2009-08-06
  • 录用日期:2009-08-28
  • 在线发布日期: 2009-10-26
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