顺铂通过降低内皮和平滑肌含量并诱导大鼠海绵体神经衰老导致勃起功能障碍。
Cisplatin causes erectile dysfunction by decreasing endothelial and smooth muscle content and inducing cavernosal nerve senescence in rats.
机构信息
Department of Urology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China.
Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China.
出版信息
Front Endocrinol (Lausanne). 2023 Jan 25;14:1096723. doi: 10.3389/fendo.2023.1096723. eCollection 2023.
INTRODUCTION
Cisplatin (cis-diamminedichloroplatinum II, CDDP), a drug widely used for cancer worldwide, may affect erectile function, but its side effects have not received enough attention. To investigate the effect of CDDP on erectile function and its possible mechanism.
METHODS
Sprague-Dawley rats were intraperitoneally administered CDDP (CDDP group) or the same volume of normal saline (control group). Erectile function was evaluated after a one-week washout. Then, histologic changes in the corpus cavernosum and cavernous nerve (CN) were measured. Other Sprague-Dawley rats were used to isolate the major pelvic ganglion and cavernous nerve (MPG/CN). RSC96 cells were then treated with CDDP. SA-β-gal staining was used to identify senescent cells, and qPCR was used to detect the senescence-associated secretory phenotype (SASP). Finally, the supernatant of RSC96 cells was used to culture MPG/CN. Erectile function was measured after administration of CDDP. The cavernosum levels of α-SMA, CD31, eNOS, and γ-H2AX, the apoptosis rate and the expression of p16, p21 and p53 in CN were also assayed. The senescent phenotype of RSC96 cells treated with CDDP was identified, and neurite growth from the MPG/CN was photographed and measured.
RESULTS
The CDDP group had a significantly lower ICP/MAP ratio than the control group. Compared to the control group, the CDDP group exhibited significantly lower α-SMA, CD31 and eNOS levels and significantly higher γ-H2AX and apoptosis rates in corpus cavernosum. In addition, CDDP increased some senescence markers p16, p21 and p53 in CN. , CDDP induced RSC96 senescence and SASP, and the supernatant of senescent cells slowed neurite outgrowth of MPG/CN.
DISCUSSIONS
CDDP treatment could induce erectile dysfunction, by affecting the content of endothelial and smooth muscle and causing SASP in CN. The results indicate that CDDP treatment should be considered as a risk factor for ED. Clinicians should pay more attention to the erectile function of cancer patients who receive CDDP treatment.
简介
顺铂（cis-diamminedichloroplatinum II，CDDP）是一种广泛用于全球癌症治疗的药物，可能会影响勃起功能，但它的副作用尚未得到足够的重视。本研究旨在探讨 CDDP 对勃起功能的影响及其可能的机制。
方法
SD 大鼠腹腔内给予 CDDP（CDDP 组）或等体积生理盐水（对照组），一周洗脱期后评估勃起功能。然后测量海绵体组织和海绵体神经（CN）的组织学变化。另取 SD 大鼠分离主要盆神经节和海绵体神经（MPG/CN）。然后用 CDDP 处理 RSC96 细胞。用 SA-β-gal 染色鉴定衰老细胞，用 qPCR 检测衰老相关分泌表型（SASP）。最后，用 RSC96 细胞上清液培养 MPG/CN，给予 CDDP 后测量勃起功能。还检测了 CN 中 α-SMA、CD31、eNOS 和 γ-H2AX 的水平、凋亡率以及 p16、p21 和 p53 的表达。鉴定了 CDDP 处理后的 RSC96 细胞的衰老表型，并拍摄和测量了 MPG/CN 的神经突生长情况。
结果
CDDP 组的 ICP/MAP 比值明显低于对照组。与对照组相比，CDDP 组海绵体组织中 α-SMA、CD31 和 eNOS 水平明显降低，γ-H2AX 和凋亡率明显升高。此外，CN 中 CDDP 增加了一些衰老标志物 p16、p21 和 p53。CDDP 诱导 RSC96 衰老和 SASP，衰老细胞的上清液减缓 MPG/CN 的神经突生长。
讨论
CDDP 治疗可能通过影响内皮和平滑肌的含量并导致 CN 中的 SASP 引起勃起功能障碍。结果表明，CDDP 治疗应被视为 ED 的一个危险因素。临床医生应更加关注接受 CDDP 治疗的癌症患者的勃起功能。
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