塞来昔布对压力性尿失禁模型大鼠的效果及作用机制

Effects and mechanism of celecoxib on model rats of stress urinary incontinence

目的研究塞来昔布对压力性尿失禁模型大鼠的干预效果及作用机制。方法建立压力性尿失禁大鼠模型后分为模型组和塞来昔布组各18只,正常组10只。塞来昔布组大鼠采用塞来昔布进行干预,模型组和正常组大鼠采用等体积的无菌蒸馏水干预,设置喷嚏试验、检测尿流动力学指标,然后测定漏尿点压力(LPP)、腹部漏尿点压力(ALPP),观察3组大鼠病理形态学特征,Western blot检测转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)通路蛋白表达,酶联免疫吸附试验法检测环氧化酶2(COX-2)、脂肪氧化酶(LOX)、基质金属蛋白酶-2(MMP-2)蛋白水平。结果喷嚏实验阳性率模型组66.67%,显著大于塞来昔布组的27.78%,差异具有显著性统计学意义(P<0.05);LPP、ALPP、TGF-β1、CTGF水平及LOX蛋白水平均为模型组<塞来昔布组<正常组(P均<0.05),COX-2、MMP-2蛋白水平均为模型组>塞来昔布组>正常组(P均<0.05)。结论塞来昔布对压力性尿失禁模型大鼠的治疗效果显著,通过调控TGF-β1/CTGF通路蛋白,可以改善大鼠COX-2、LOX、MMP-2水平,对于治疗和预防压力性尿失禁的研究提供了方向。

Objective To explore the effects and mechanism of celecoxib on stress urinary incontinence in rats.Methods Rat models of stress urinary incontinence were established and divided into model group(n=18),celecoxib group(n=18)and normal group(n=10).Rats in celecoxib group were intervened with celecoxib.Rats in model group and normal group were intervened with sterile distilled water of equal volume.The urodynamic indexes were detected with sneeze test.Then the pressure of leaking point(LPP)and abdominal leaking point(ALPP)were measured.The pathomorphological characteristics were observed.The expressions of transforming growth factor-β1(TGF-β1)and connective tissue growth factor(CTGF)pathway protein were determined with Western blot.The levels of cyclooxygenase-2(COX-2),lipid oxidase(LOX),and matrix metalloproteinase-2(MMP-2)were detected with enzyme-linked immunosorbent assay.Results The positive rate of sneezing test was higher in model group than in celecoxib group(66.67%vs.27.78%,P<0.05).The levels of LPP,ALPP TGF-β1,CTGF and LOX were model group<celecoxib group<normal group(all P<0.05).The levels of COX-2 and MMP-2 were model group>celecoxib group>normal group(all P<0.05).Conclusion Celecoxib has a significant effect on model rats of stress urinary incontinence.Regulating the TGF-β/CTGF pathway protein can improve the levels of COX-2,LOX and MMP-2 in rats,which provides a direction for research on the treatment and prevention of stress urinary incontinence.