Pu Xiao-Yong, Wang Xing-Huan, Gao Wai-Chen, Yang Zhong-Hua, Li Shi-Lin, Wang Huai-Peng, Wu Yi-Long
Guangdong Provincial People's Hospital-Department of Urology, Cancer Center and The Medical Research Center, Guangdong, Guangzhou, China.
J Sex Med. 2008 Jun;5(6):1345-54. doi: 10.1111/j.1743-6109.2008.00817.x. Epub 2008 Mar 19.
Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks.
To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat.
Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined.
Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 microg/kg (N = 10) and IGF-1 10 microg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3',5'-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed.
After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 microg/kg and the IGF-1 10 microg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats.
IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways.
胰岛素样生长因子-1（IGF-1）是具有广泛生物学效应的生长因子之一。我们已证实将IGF-1基因转移至阴茎可改善勃起功能。然而，基因治疗存在一些局限性，如毒性或插入诱变风险。蛋白质治疗可能是降低这些风险的另一种选择。
研究阴茎海绵体内注射IGF-1蛋白是否能恢复衰老大鼠的勃起功能。
测定勃起反应、形态学变化以及与一氧化氮-环磷酸鸟苷（NO-cGMP）信号通路相关的标志物。
本研究纳入10只年轻（4个月）和30只老年（24个月）的Sprague-Dawley雄性大鼠。老年大鼠分为三组：仅注射溶剂组（N = 10）、1微克/千克IGF-1组（N = 10）和10微克/千克IGF-1治疗组（N = 10）。在单次注射IGF-1治疗4周和8周后，评估海绵体神经电刺激引起的海绵体内压（ICP）反应。还评估了海绵体组织中平滑肌的百分比、内皮型一氧化氮合酶（eNOS）的mRNA和蛋白表达。分析了阴茎组织中作用于主要NO-cGMP信号通路的一氧化氮合酶（NOS）活性和环磷酸鸟苷（cGMP）浓度。
与仅注射溶剂组相比，在4周和8周时，IGF-1 1微克/千克组和IGF-1 10微克/千克组经IGF-1治疗后的ICP反应均显著增加，与年轻对照组相当（P < 0.05）。Masson三色染色显示IGF-1治疗组海绵体平滑肌百分比增加。IGF-1增加了e-NOS表达。IGF-1治疗的大鼠中NOS活性和cGMP浓度也显著增加。
IGF-1通过恢复海绵体平滑肌的完整性和调节NO-cGMP通路改善了老年大鼠的勃起功能。
