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金纳米粒子处理对睾酮诱导的大鼠良性前列腺增生的影响。

Effect of gold nanoparticles treatment on the testosterone-induced benign prostatic hyperplasia in rats.

机构信息

Department of Biological Sciences, Yarmouk University, Irbid, Jordan.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.

出版信息

Int J Nanomedicine. 2019 May 3;14:3145-3154. doi: 10.2147/IJN.S202645. eCollection 2019.

Abstract

Gold nanoparticles (AuNps) are promising agents for prostate cancer therapy. Herein, the in vivo effects of 20 and 50 nm sized AuNps on experimentally induced benign prostatic hyperplasia (BPH) was examined. Adult male rats were divided into four groups (n=6-8 each). A negative control group and three groups were injected daily with testosterone (3 mg/kg/subcutaneously) to induce BPH. Animals receiving testosterone were randomized to untreated BPH group and two BPH groups which were treated intraperitoneally with 20 and 50 nm AuNps (5 mg/kg/daily) in addition to testosterone. After three weeks, histopathological changes and serum levels of testosterone and dihydrotestosterone (DHT) were analyzed. In addition, the prostate tissue levels of transforming growth factor-β (TGF-β), vascular endothelial growth factor-a (VEGF-A) and interleukin-6 (IL-6) were measured using ELISA. There were significant increases in the prostate weight/body weight ratio, serum testosterone and DHT and in the prostate tissue content of TGF-β, IL-6 and VEGF-A in the untreated BPH group. histological examination showed morphological abnormalities with more proliferation in the glandular epithelial and stromal area and with abundant epithelial papillary folds in the BPH group. Simultaneous administration of 50 nm AuNps with testosterone tended to increase the prostate weight/body weight ratio and increase the tissue level of IL-6 in compared to the BPH group. Conversely, treatment with 20 nm AuNps significantly reduced the elevated tissue content of TGF-β, IL-6, and VEGF-A. Histopathological examination also showed that 20 nm but not the 50 nm AuNps administration ameliorates testosterone-induced prostatic hyperplasia. In experimentally induced BPH, AuNps can inhibit the progression of BPH in a size-dependent manner. while 20 nm AuNps ameliorate BPH by its inhibitory effects on the prostatic cell proliferation, inflammation and angiogenesis, the 50 nm AuNps could potentially exacerbate the development of BPH in rats, mainly through enhancing the inflammatory process.

摘要

金纳米粒子(AuNps)是治疗前列腺癌的有前途的药物。在此,研究了 20nm 和 50nm 大小的 AuNps 对实验性诱导的良性前列腺增生(BPH)的体内影响。成年雄性大鼠分为四组(每组 6-8 只)。阴性对照组和三组每天皮下注射睾酮(3mg/kg)诱导 BPH。接受睾酮的动物随机分为未治疗 BPH 组和两个 BPH 组,这两个 BPH 组除了接受睾酮外,还通过腹膜内注射 20nm 和 50nm AuNps(5mg/kg/天)进行治疗。三周后,分析组织病理学变化以及血清睾酮和二氢睾酮(DHT)水平。此外,使用 ELISA 测量前列腺组织中转化生长因子-β(TGF-β)、血管内皮生长因子-a(VEGF-A)和白细胞介素-6(IL-6)的水平。未治疗 BPH 组的前列腺重量/体重比、血清睾酮和 DHT 以及前列腺组织中 TGF-β、IL-6 和 VEGF-A 的含量均显著增加。组织学检查显示 BPH 组腺体上皮和基质区增生更多,上皮乳头状褶皱丰富,形态异常。与 BPH 组相比,同时给予睾酮和 50nm AuNps 治疗时,前列腺重量/体重比增加,组织中 IL-6 水平升高。相反,用 20nm AuNps 治疗可显著降低升高的 TGF-β、IL-6 和 VEGF-A 组织含量。组织学检查还显示,20nm AuNps 而非 50nm AuNps 可改善睾酮诱导的前列腺增生。在实验性诱导的 BPH 中,AuNps 可以以大小依赖的方式抑制 BPH 的进展。虽然 20nm AuNps 通过抑制前列腺细胞增殖、炎症和血管生成来改善 BPH,但 50nm AuNps 可能会通过增强炎症过程而加重大鼠的 BPH 发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ecc/6507074/f8c51264b843/IJN-14-3145-g0001.jpg

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