通过抗氧化疗法恢复糖尿病大鼠的勃起功能。
Restoring erectile function by antioxidant therapy in diabetic rats.
作者信息
Hirata Hiroshi, Kawamoto Ken, Kikuno Nobuyuki, Kawakami Toshifumi, Kawakami Kazumori, Saini Sharanjot, Yamamura Soichiro, Dahiya Rajvir
机构信息
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, California 94121, USA.
出版信息
J Urol. 2009 Nov;182(5):2518-25. doi: 10.1016/j.juro.2009.07.009. Epub 2009 Sep 17.
PURPOSE
Diabetes mediates an increase in reactive oxygen species that can lead to impaired endothelial function, decreased smooth muscle in the diabetic corpus cavernosum and increased apoptosis. We hypothesized that antioxidant therapy may restore erectile function by inhibiting apoptosis in diabetic rat crura.
MATERIALS AND METHODS
A total of 40 male Sprague-Dawley rats were randomized to 5 groups of 8 each, including healthy controls, rats with diabetes, and rats with diabetes with the antioxidant tempol (4-hydroxytetramethyl-piperidine-1-oxyl) (Sigma-Aldrich), with insulin, and with tempol and insulin. Intracavernous pressure was measured for functional analysis. Smooth muscle and collagen fiber levels in the rat penile corpus cavernosum were assessed by hematoxylin and eosin, and Masson's trichrome staining. Endothelial cells were assessed by CD31 staining. Reactive oxygen species related genes were analyzed by cDNA microarray. We confirmed mRNA and protein expression profiles for these genes in diabetic and treated rats using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. TUNEL assay was done to analyze apoptosis status.
RESULTS
Intracavernous pressure in diabetic rats was significantly decreased vs controls. After treatment with tempol or insulin alone intracavernous pressure was significantly increased compared to that in untreated diabetic rats. In the diabetic group mean smooth muscle area significantly decreased but was restored after combined tempol and insulin. Endothelial cell area in diabetic rats significantly decreased and was not restored by any treatments. However, apoptosis was restored to normal by combined insulin and tempol. Of 84 reactive oxidative stress and antioxidant genes 32 were identified specific to diabetic rats compared to healthy controls. UCP3 expression was significantly increased in diabetic rats and normal levels were restored by all treatments.
CONCLUSIONS
To our knowledge this is the first report that tempol and insulin can restore erectile function in diabetic rats by inhibiting apoptosis.
目的
糖尿病介导活性氧增加，这可导致内皮功能受损、糖尿病海绵体平滑肌减少及细胞凋亡增加。我们假设抗氧化治疗可通过抑制糖尿病大鼠海绵体脚细胞凋亡来恢复勃起功能。
材料与方法
总共40只雄性Sprague-Dawley大鼠被随机分为5组，每组8只，包括健康对照组、糖尿病大鼠组、糖尿病大鼠加抗氧化剂tempol（4-羟基四甲基哌啶-1-氧基）（Sigma-Aldrich）组、糖尿病大鼠加胰岛素组以及糖尿病大鼠加tempol和胰岛素组。测量海绵体内压进行功能分析。通过苏木精-伊红染色和Masson三色染色评估大鼠阴茎海绵体中的平滑肌和胶原纤维水平。通过CD31染色评估内皮细胞。通过cDNA微阵列分析活性氧相关基因。我们使用实时逆转录聚合酶链反应和免疫组织化学确认了糖尿病大鼠和治疗后大鼠中这些基因的mRNA和蛋白质表达谱。进行TUNEL分析以分析细胞凋亡状态。
结果
与对照组相比，糖尿病大鼠的海绵体内压显著降低。单独用tempol或胰岛素治疗后，与未治疗的糖尿病大鼠相比，海绵体内压显著升高。糖尿病组的平均平滑肌面积显著减少，但在tempol和胰岛素联合治疗后恢复。糖尿病大鼠的内皮细胞面积显著减少，且任何治疗均未使其恢复。然而，胰岛素和tempol联合使用可使细胞凋亡恢复正常。与健康对照组相比，在84个活性氧化应激和抗氧化基因中，有32个被鉴定为糖尿病大鼠特有的基因。UCP3表达在糖尿病大鼠中显著增加，所有治疗均使其恢复到正常水平。
结论
据我们所知，这是第一份关于tempol和胰岛素可通过抑制细胞凋亡恢复糖尿病大鼠勃起功能的报告。
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