目的:观察塞来昔布(celecoxih,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(3mg·kg^-1·d^-1)、大剂量(10mg·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COX2[(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〈0.053。结论:3、10mg·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。
Objective:To investigate the effect of celecoxib (CXB),a specific COX-2 inhibitor,on the proliferation of Han: SPREV-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 coexpression 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 ± 0.261, [2.8 ± 0.31] vs E3.7 ± 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. 0121, 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.