Effects of Icariin on Improving Erectile Function in Streptozotocin-Induced Diabetic Rats
Effects of Icariin on Improving Erectile Function in Streptozotocin-Induced Diabetic Rats
复制标题
淫羊藿苷对改善链脲佐菌素诱导的糖尿病大鼠勃起功能的作用。
DOI：
10.1111/j.1743-6109.2011.02421.x
复制
发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Xin, Zhong-Cheng
中科院分区：
文献类型：
--
作者：
Liu, Tao;Xin, Hua;Xin, Zhong-Cheng
介绍
在海绵体神经损伤和去势所致勃起功能障碍的动物模型中，淫羊藿苷已被证明可改善阴茎血流动力学。淫羊藿苷对糖尿病动物阴茎血流动力学的影响仍有待确定。转化生长因子β 1（transforming growth factor β 1，TGF β 1）与糖尿病相关性勃起功能障碍的发病机制有关。
目的
本研究旨在探讨淫羊藿苷对链脲佐菌素（STZ）诱导的糖尿病大鼠阴茎的影响。
方法
两个月大的Sprague-Dawley雄性大鼠在禁食16小时后接受一次性腹膜内（IP）STZ（60 mg/kg）或溶媒注射。3天后，将STZ诱导的糖尿病大鼠随机分为4组，每天灌胃1、5和10 mg/kg的生理盐水和二甲基亚砜（DMSO）或溶于DMSO中的淫羊藿苷，连续3个月。阳性对照组IP注射生理盐水，然后每日灌胃生理盐水/DMSO溶液。在功能测定和安乐死前1周停止处理。
主要观察指标
通过电刺激海绵体神经并实时测量海绵体内压（ICP）来评估阴茎血流动力学。安乐死后，使用免疫组织化学、Western印迹和酶联免疫吸附试验（ELISA）研究阴茎组织，以评估一氧化氮-环磷酸鸟苷（NO-cGMP）和TGF β 1/Smad2信号通路。
结果
糖尿病减弱对照动物的ICP反应。未治疗的糖尿病动物海绵体中的平滑肌/胶原蛋白比率和内皮细胞含量降低;用淫羊藿苷治疗可部分减弱这些作用。淫羊藿苷治疗的动物也有一个显着更大的表达烟酰胺腺嘌呤二核苷酸磷酸阳性神经和内皮细胞标志物，血管性血友病因子（vWF）和血小板内皮细胞粘附分子-1（PECAM）。与阴性对照组相比，淫羊藿苷处理组大鼠阴茎中TGF β 1/Smad2信号通路表达下调。
结论
淫羊藿苷治疗保护了糖尿病大鼠阴茎的血流动力学、平滑肌和内皮的完整性以及神经元型一氧化氮合酶的表达。TGF β 1/Smad2信号通路的下调可能介导了这种作用。
INTRODUCTION
Icariin has been shown to improve penile hemodynamics in animal models of erectile dysfunction from cavernous nerve injury and castration. The effects of icariin on penile hemodynamics in diabetic animals remain to be determined. Transforming growth factor β1 (TGFβ1) has been implicated in the pathogenesis of diabetes-related erectile dysfunction.
AIM
The aim of this study was to investigate the effects of icariin in the penis of streptozotocin (STZ)-induced diabetic rat.
METHODS
Two-month-old Sprague-Dawley male rats received one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16-hour fast. Three days later, the STZ-induced diabetic rats were randomly divided into four groups and were treated with daily gavage feedings of a 50:50 mix of normal saline and dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO at doses of 1, 5, and 10 mg/kg for 3 months. A positive control group underwent IP injection of saline followed by daily gavage of saline/DMSO solution. Treatment was stopped 1 week prior to functional assay and euthanasia.
MAIN OUTCOME MEASURE
Penile hemodynamics was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was studied using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay (ELISA) to assess the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and TGFβ1/Smad2 signaling pathway.
RESULTS
Diabetes attenuated ICP response in control animals. Untreated diabetic animals had decreased smooth muscle/collagen ratio and endothelial cell content in the corpora cavernosa; treatment with icariin partially attenuating these effects. Icariin-treated animals also had a significantly greater expression of nicotinamide adenine dinucleotide phosphate-positive nerves and the endothelial cell markers, von Willebrand factor (vWF), and platelet endothelial cell adhesion molecule-1 (PECAM). TGFβ1/Smad2 signaling pathway was down-regulated in the penis from icariin-treated models relative to what was observed in negative control animals.
CONCLUSION
Icariin treatment preserved penile hemodynamics, smooth muscle and endothelial integrity, and neuronal nitric oxide synthase expression in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2 signaling pathway might mediate this effect.