目的:初步探讨雌激素受体β(ERβ)对小鼠阴茎血管内皮的保护作用。方法:随机选取E邸基因敲除(ERβKO)雄性小鼠和相应野生型雄性小鼠各12只,随机分为±组:正常对照组、ERβKO组、野生型+TNFα处理组和ERβKO+TNFα处理组。ERβKO组及正常对照组腹腔注射生理盐水,野生型+TN凡处理组和ERβKO+TNFα处理组给予TNFα6μg/(kg·d)腹腔注射,连续1±d。观察阿朴吗啡诱导的自发勃起反应;制备阴茎组织切片,内皮细胞标志物CD34、vWF免疫组化染色观察海绵窦内皮细胞变化,TUNEL法检测海绵体组织细胞凋亡情况。结果:与正常对照组相比,ERβKO组勃起潜伏期延长(P〈0.05),但勃起次数无显著差异;ERβKO+TNFα组与野生型+TNFα组潜伏期显著延长(P〈0.05),勃起次数显著减少(P〈0.05),以ERβKO+TNFα组变化更显著。免疫组化结果显示,与正常对照组(CD34:3.00±0.00,vWF:2.75±0.50)比较,海绵体组织CD34、vWF蛋白表达在ERβKO组(CD34:2.25±0.50,vWF:2.00±0.00)、ERDKO+TNFα组(CD34:0.25±0.50,vWF:0.33±0.58)、野生型+TNFα组(CD34:1.50±0.58,vWF:1.25±0.50)均显著减少(P〈0.05),且ERβKO+TNFα组比野生型+TNFα组减少更显著(P〈0.05)。仅在ERISKO+TNFα组海绵体发现凋亡细胞。结论:E邸基因敲除后,尤其在内皮损伤因素TNFα作用下,小鼠阴茎血管内皮细胞减少,提示ERD对阴茎海绵窦内皮具有保护效应。
Objective: To investigate the protective effect of ERβ on the penile vascular endothelium in mice. Methods: We randomly selected 12 EPβ knockout (ERβKO) and 12 C57BL/ 6 male mice, and divided them into four groups: normal control, ERβKO, ERβKO + TNFα, and wild-type + TNFα group. The former two were treated with normal saline, while the latter two by intraperitoneal injection of TNFα at 6 μg/( kg · d) for 14 days. Then we observed the spontaneous erectile response induced by APO and changes of the endothelial cells by immunohistochemical staining of CD34 and vWF, and detected cell apoptosis in the penile cavernous tissue by TUNEL. Results: Compared with the normal control group, the ERβKO group showed significantly increased erectile latency (P 〈 0.05), but no significant difference in the number of erections ; the ERβKO + TNFα and wild-type + TNFα groups, too, exhibited remarkably longer erectile latency ( P 〈0.05 ) but fewer erections ( P 〈 0.05 ), with even more obvious changes in the ERβKO + TNFα group. The expressions of CD34 and vWF were significantly reduced in the ERβKO group (2.25 ±0.50 and 2.00 ± 0.00), ERβKO + TNFα group (0.25 ±0.50 and 0.33± 0.58) and wild-type + TNFα group ( 1.50 ±0.58 and 1.25 +0.50) as compared with those in the control ( 3.00 ± 0.00 and 2.75 ± 0.50) ( P 〈 0.05 ), even lower in the ERβKO + TNFα than in the wild- type + TNFα group ( P 〈 0.05 ). Apoptotie cells were found only in the ERβKO + TNFα group. Conclusion : After ERβ knockout and especially after treated with the endothelial injury factor TNFα, endothelial cells are decreased in the penile vessels in mice, which suggests that ERβ has a protective effect on the penile cavernous sinus endothelium. Natl J Androl, 2012, 18 (3) : 216 -221