Refaie Marwa M M, Rifaai Rehab A, Zenhom Nagwa M
Department of Pharmacology, Faculty of Medicine, Minia University, 61511, Minia, Egypt.
Department of Histology, Faculty of Medicine, Minia University, 61511, Minia, Egypt.
Fundam Clin Pharmacol. 2018 Dec;32(6):617-626. doi: 10.1111/fcp.12384. Epub 2018 Jun 28.
Nearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator-activated receptor alpha (PPARα) had protective effect in different models, but still, there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3 mg/kg/day for 4 weeks) subcutaneous injection followed by FEN (300 mg/kg/day) was given orally for 4 weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Prostate-specific antigen (PSA), dihydrotestosterone (DHT), and total antioxidant capacity (TAC) in serum were determined. The mRNA gene expressions of proliferating cell nuclear antigen (PCNA), PPARα, and glutathione peroxidase (GPx) in prostatic tissue were also measured by quantitative real-time polymerase chain reaction. In addition, the histopathological changes and activated caspase3 immunoexpression were evaluated. Our results showed that TP succeeded in induction of BPH, which was detected by significant increase in prostate weights, prostatic tissue MDA, serum levels of DHT, PSA, and mRNA gene expression of PCNA but significant decrease in PPARα and GPx gene expression. Moreover, TAC in serum and SOD level in prostate tissue decreased. The histopathological examination showed typical changes of BPH with dysplastic changes with marked decrease in activated caspase3 immunoexpression indicating marked suppression of the apoptotic process. FEN significantly improved all disturbed parameters of BPH model. Moreover, there are no dysplastic changes with co-administration of FEN to BPH induced group.
几乎所有达到平均预期寿命的男性都患有前列腺疾病。最常见的是良性前列腺增生（BPH）。过氧化物酶体增殖物激活受体α（PPARα）在不同模型中具有保护作用，但仍没有研究解释其在BPH中的作用。因此，我们研究了非诺贝特（FEN）对丙酸睾酮（TP）（3mg/kg/天，共4周）皮下注射诱导的BPH的影响，随后口服FEN（300mg/kg/天），持续4周。我们测量了前列腺重量变化、前列腺组织超氧化物歧化酶（SOD）和丙二醛（MDA）水平。测定了血清中的前列腺特异性抗原（PSA）、二氢睾酮（DHT）和总抗氧化能力（TAC）。还通过定量实时聚合酶链反应测量了前列腺组织中增殖细胞核抗原（PCNA）、PPARα和谷胱甘肽过氧化物酶（GPx）的mRNA基因表达。此外，评估了组织病理学变化和活化的半胱天冬酶3免疫表达。我们的结果表明，TP成功诱导了BPH，这通过前列腺重量、前列腺组织MDA、血清DHT水平、PSA以及PCNA的mRNA基因表达显著增加得以检测，但PPARα和GPx基因表达显著降低。此外，血清中的TAC和前列腺组织中的SOD水平降低。组织病理学检查显示BPH的典型变化伴有发育异常变化，活化的半胱天冬酶3免疫表达显著降低，表明凋亡过程受到明显抑制。FEN显著改善了BPH模型中所有受干扰的参数。此外，FEN与BPH诱导组联合给药时没有发育异常变化。
