摘要
【目的】探讨非那雄胺对大鼠良性前列腺增生(BPH)致下尿路症状的影响及作用机制。【方法】30只大鼠分为假手术组、模型组和非那雄胺组,每组10只。模型组和非那雄胺组采用去势+注射丙酸睾酮制备BPH模型,假手术组未去势,注射等量芝麻油,建模成功后,非那雄胺组灌胃非那雄胺0.8 mg/kg,模型组和假手术组灌胃生理盐水,持续灌胃28 d。末次灌胃后检测各组排尿情况;处死大鼠,计算前列腺指数、膀胱指数,HE染色观察前列腺和膀胱组织病理学变化,Masson染色观察膀胱组织胶原纤维沉淀情况,TUNEL检测膀胱逼尿肌细胞凋亡率;Western blot检测膀胱组织中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、白细胞介素-1β(IL-1β)、含半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1)蛋白相对表达量。【结果】与假手术组相比,模型组前列腺指数、膀胱指数、排尿频率、残余尿量均升高(P<0.05),排尿总量无变化(P>0.05);与模型组比较,非那雄胺组前列腺指数、膀胱指数排尿频率、残余尿量均降低(P<0.05),排尿总量无变化(P>0.05)。HE染色显示:模型组前列腺组织明显增生,膀胱组织固有膜结缔组织增生,黏膜增厚,大量膀胱上皮细胞呈乳头状增生;非那雄胺组前列腺和膀胱组织病理学均显著改善。与假手术组相比,模型组膀胱逼尿肌细胞凋亡率、胶原纤维阳性面积占比及膀胱组织中NLRP3、IL-1β、Caspase-1蛋白相对表达量升高(P<0.05);与模型组比较,非那雄胺组膀胱逼尿肌细胞凋亡率、胶原纤维阳性面积占比、膀胱组织中NLRP3、IL-1β、Caspase-1蛋白相对表达量降低(P<0.05)。【结论】非那雄胺可有效改善大鼠BPH导致的下尿路症状,抑制膀胱逼尿肌细胞凋亡,其机制可能与NLRP3/Caspase-1信号通路有关。
【Objective】To investigate the effect and mechanism of finasteride on lower urinary tract symptoms(LUTS)caused by benign prostatic hyperplasia(BPH)in rats.【Methods】Thirty rats were divided into sham operation group,model group,and finasteride group,with 10 rats in each group.The model group and finasteride group were used to establish BPH models by castration plus injection of testosterone propionate,while the sham operation group was not castrated and injected with an equal amount of sesame oil.After successful modeling,the finasteride group was intragastrically administered with finasteride at 0.8 mg/kg,and the model group and sham operation group were intragastrically administered with normal saline for 28 consecutive days.After the last gavage,the urination status of each group was detected;the rats were sacrificed to calculate the prostate index and bladder index.HE staining was used to observe the histopathological changes of prostate and bladder tissues,Masson staining to observe the collagen fiber deposition in bladder tissues,and TUNEL method to detect the apoptosis rate of bladder detrusor cells.Western blot was used to detect the relative expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),interleukin-1β(IL-1β),and cysteine-aspartic acid protease-1(Caspase-1)in bladder detrusor.【Results】Compared with the sham operation group,the prostate index,bladder index,micturition frequency,and residual urine volume in the model group were increased(P<0.05),while the total urine volume had no change(P>0.05).Compared with the model group,the prostate index,bladder index,micturition frequency,and residual urine volume in the finasteride group were decreased(P<0.05),and the total urine volume had no change(P>0.05).HE staining showed that the prostate tissue in the model group had obvious hyperplasia,the lamina propria connective tissue of the bladder tissue was hyperplastic,the mucosa was thickened,and a large number of bladder epithelial cells showed papillary hyperplasia;the histopathology of the prostate and bladder tissues in the finasteride group was significantly improved.Compared with the sham operation group,the apoptosis rate of bladder detrusor cells,the positive area ratio of collagen fibers,and the relative expression levels of NLRP3,IL-1β,and Caspase-1 proteins in bladder tissues in the model group were increased(P<0.05).Compared with the model group,the apoptosis rate of bladder detrusor cells,the positive area ratio of collagen fibers,and the relative expression levels of NLRP3,IL-1β,and Caspase-1 proteins in bladder tissues in the finasteride group were decreased(P<0.05).【Conclusion】Finasteride can effectively improve LUTS caused by BPH in rats and inhibit the apoptosis of bladder detrusor cells,and its mechanism may be related to the NLRP3/Caspase-1 signaling pathway.
作者
魏超
丁玉峰
WEI Chao;DING Yufeng(Department of Urology,Luyi County People's Hospital,Zhoukou Henan 477200)
出处
《医学临床研究》
2025年第6期1011-1014,1018,共5页
Journal of Clinical Research
关键词
前列腺增生
雄甾烯类
大鼠
疾病模型
动物
下尿路症状
Prostatic Hyperplasia
Androstenes
Rats
Disease Models,Animal
Lower Urinary Tract Symptoms
