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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(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、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 observe the effect of celecoxib (CXB) on the growth of renal cysts in autosomal dominant polycystic kidney disease (ADPKD) model Han: SPRD rats and to explore its possible mechanism. Methods: The 3-week-old heterozygous (cy / +) Han: SPRD rats were randomly divided into 3 groups (n = 19): low dose (3mg · kg-1.d-1) and high dose (10mg · kg-1) d-1) CXB-treated group and blank control group. Rats were housed until 16 weeks of age and weighed (TBW) and renal weight (2K), calculated 2K / TBW; take kidney tissue HE staining and special staining to observe the degree of infiltration of renal interstitial cells, cyst index , And fibrosis index. The expression of COX-2 and proliferating cell nuclear antigen (PCNA) co-staining were detected by immunofluorescence confocal scanning. Western blotting was used to detect the expression of COX-2 , PCNA protein expression level. Results: The 2K / TBW of low dose CXB group was lower than that of the blank control group, the difference was statistically significant [(1.10 ± 0.009)% vs (1.33 ± 0.02)%, P <0.05]. Compared with the blank control group, the infiltration rate of interstitial cells of renal interstitial cells in the low-dose and high-dose CXB groups was relieved ([2.6 ± 0.26], (2.8 ± 0.31) vs (3.7 ± 0.33), P <0.05] Renal cyst index (42.9 ± 6.56, 47.1 ± 7.28 vs 64.8 ± 6.71) and fibrosis index (11.2 ± 2.63, 10.1 ± 3.30 vs 16.3 ± 4.16, P < 0.05). Compared with the blank control group, the intensity of COX-2 and PCNA co-staining in the low-dose CXB group was significantly weaker than that in the blank control group (P <0.05). Compared with the blank control group, the small- and high-dose Compared with the control group, the expression of COX-2 in the CXB-treated group was significantly lower than that in the CXCL-treated group (0.326 ± 0.011 vs 0.409 ± 0.008 vs 0.814 ± 0.012, P <0.05) ) vs (0.988 ± 0.031), P <0.05]. Conclusion: Celecoxib at 3, 10 mg · kg-1.d-1 may play an important role in inhibiting the growth of renal cysts in Han: SPRD rats by inhibiting COX-2 activity and reducing inflammatory cell infiltration.