Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats.
Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats.
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DOI：
10.1016/j.esxm.2021.100484
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发表时间：
2022-04
期刊：
影响因子：
2.6
通讯作者：
Kimura, Kazunori
中科院分区：
文献类型：
--
作者：
Kataoka, Tomoya;Kawaki, Yuto;Kito, Yohei;Suzuki, Jun;Mori, Taiki;Hotta, Yuji;Sanagawa, Akimasa;Kawade, Yoshihiro;Maeda, Yasuhiro;Furukawa-Hibi, Yoko;Kimura, Kazunori
已知含铂抗癌剂奥沙利铂（L-OHP）会诱发周围神经病变，包括勃起功能障碍（艾德）作为副作用，而Gosha-jinki-gan（GJG）是主要用于周围神经病变的传统日本草药。目的：观察固精颗粒对L-OHP诱导的大鼠艾德性ED的影响。将10周龄雄性Wister/ST大鼠分为以下组：假手术组、假手术+GJG组、L-OHP组和L-OHP+GJG组（每组n = 10）。L-OHP组和L-OHP+GJG组于第1周连续2天静脉注射L-OHP（4 mg/kg）。使用Bonferroni多重比较检验确定统计学显著性。在研究期结束时，通过测量海绵体神经刺激后的海绵体内压（ICP）和平均动脉压（MAP）来评估勃起功能。Western blot分析用于评估神经元型一氧化氮合酶（nNOS）和内皮型一氧化氮合酶（eNOS）水平，定量聚合酶链反应用于评估磷酸二酯酶-5（PDE-5）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶-1的表达。L-OHP组ICP/MAP比值（0.34 ± 0.06）显著低于Sham组（0.67 ± 0.03，P <0.01），而L-OHP+GJG组ICP/MAP比值（0.55 ± 0.01）显著高于L-OHP组（P <0.01）。两组间nNOS和eNOS蛋白表达差异无统计学意义（P > 0.05）。GJG给药显著降低L-OHP+GJG组PDE-5和NADPH氧化酶-1 mRNA的表达。这项动物模型研究表明，GJG可能对癌症幸存者的勃起功能有效。我们的研究表明，GJG在治疗组中没有明显的副作用。对海绵体神经的进一步研究也有助于阐明GJG效应的机制，这是本研究的局限性。我们发现GJG给药通过改善PDE-5的转录表达来改善L-OHP诱导的艾德。Kataoka T，Kawaki Y，Kito Y，et al. Gosha-Jinki-Gan通过降低大鼠磷酸二酯酶-5的转录表达来改善抗癌剂奥沙利铂引起的勃起功能障碍。性医学2022;10：100484。
A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy. To investigate the effect of GJG on L-OHP-induced ED in rats. Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test. At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1. The ICP/MAP ratio of L-OHP rats (0.34 ± 0.06) was significantly lower than that of Sham rats (0.67 ± 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 ± 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group. This animal model study suggests that GJG might be effective for erectile function in cancer survivors. Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study. We found that GJG administration improved L-OHP-induced ED by improving transcriptional PDE-5 expression. Kataoka T, Kawaki Y, Kito Y, et al. Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats. Sex Med 2022;10:100484.
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