Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku, Japan.
Life Sci. 2021 Feb 1;266:118924. doi: 10.1016/j.lfs.2020.118924. Epub 2020 Dec 19.
We investigated the therapeutic effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs).
Male SHRs (age, 36 weeks) were perorally treated with losartan (3 or 10 mg·kg) or vehicle once daily for 18 weeks. Age-matched Wistar Kyoto rats (WKYs) were used as vehicle-treated controls (n = 8). The effects of losartan were evaluated by analyzing prostate weight, blood pressure, and prostatic blood flow. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate involved hematoxylin and eosin staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay.
Compared to the vehicle-treated WKYs, the vehicle-treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan caused significant recovery of blood flow and decreased PBR and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs.
Chronic losartan treatment could ameliorate prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might have therapeutic effects on not only hypertension but also prostatic hyperplasia in humans.
本研究旨在探讨血管紧张素Ⅱ 1 型受体阻滞剂（氯沙坦）对自发性高血压大鼠（SHR）前列腺增生的治疗作用。
36 周龄雄性 SHR 经口给予氯沙坦（3 或 10mg·kg）或载体每日 1 次，共 18 周。年龄匹配的 Wistar Kyoto 大鼠（WKYs）作为载体处理对照组（n=8）。通过分析前列腺重量、血压和前列腺血流来评估氯沙坦的作用。测量组织丙二醛（MDA）、白细胞介素-6（IL-6）和碱性成纤维细胞生长因子（bFGF）水平。对前列腺腹侧进行苏木精和伊红染色和末端转移酶介导的 dUTP 缺口末端标记（TUNEL）检测，进行组织学分析。
与载体处理的 WKYs 相比，载体处理的 SHRs 前列腺重量、前列腺重量/体重比（PBR）、血压、腺上皮面积以及前列腺腹侧组织 MDA、IL-6 和 bFGF 水平显著升高，前列腺血流显著降低。氯沙坦治疗可显著恢复 SHR 前列腺血流，降低 PBR 和腺上皮面积，降低前列腺腹侧组织 MDA、IL-6 和 bFGF 水平，但不影响血压。高剂量氯沙坦可显著降低 SHR 前列腺腹侧的血压并增加 TUNEL 阳性细胞。
慢性氯沙坦治疗可通过恢复 SHR 前列腺血流减少和诱导前列腺腹侧细胞凋亡来改善前列腺增生。氯沙坦可能不仅对高血压，而且对人类的前列腺增生都具有治疗作用。
