Effects of Icariside II on Improving Erectile Function in Rats With Streptozotocin-Induced Diabetes
Effects of Icariside II on Improving Erectile Function in Rats With Streptozotocin-Induced Diabetes
复制标题
艾卡瑞苷 II 对链脲佐菌素糖尿病大鼠勃起功能的改善作用
DOI：
10.2164/jandrol.111.015172
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发表时间：
2012-09-01
影响因子：
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通讯作者：
Xin, Zhong Cheng
中科院分区：
文献类型：
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作者：
Zhou, Feng;Xin, Hua;Xin, Zhong Cheng
淫羊藿苷和淫羊藿苷II (ICA II)是从淫羊藿中分离出来的两种活性成分，具有密切的结构关系。有证据表明淫羊藿苷可能有助于治疗勃起功能障碍 (ED)；但目前ICA II治疗ED的疗效研究还很少。我们研究了 ICA II 对改善链脲佐菌素诱导的糖尿病大鼠勃起功能的影响。将 50 只 8 周龄 Sprague-Dawley 大鼠随机分为正常对照组和糖尿病组。一次性腹腔注射链脲佐菌素（60mg/kg）诱发糖尿病。三天后，糖尿病大鼠被随机分为 4 组，包括生理盐水治疗的安慰剂组和 3 个 ICA II 治疗模型（1、5 和 10 mg/kg/d）。 3个月后，通过海绵神经电刺激（CNE）和实时体内压力评估来测量阴茎血流动力学。收获阴茎并进行随后的组织学检查（天狼星红染色、哈特弹性蛋白染色和免疫组织化学染色）和蛋白质印迹，以探索一氧化氮-环磷酸鸟苷（NO-cGMP）和转化生长因子β1（TGFβ1）/Smad2信号通路的表达。糖尿病显着减弱了对 CNE 的勃起反应。与对照组相比，糖尿病大鼠的海绵体平滑肌/胶原比率和内皮细胞含量降低。糖尿病大鼠体内I型胶原蛋白与III型胶原蛋白的比例显着降低；此外，糖尿病动物的海绵状弹性纤维断裂。神经元一氧化氮合酶（nNOS）、内皮一氧化氮合酶和血管内皮生长因子在糖尿病组中表达水平较低；与安慰剂治疗的糖尿病动物相比，ICA II 治疗的糖尿病大鼠在阴茎中的表达更高。 ICA II 治疗大鼠阴茎中 TGF beta 1/Smad2/结缔组织生长因子 (CTGF) 信号通路和细胞凋亡均下调。 ICA II 治疗可能通过增加平滑肌、内皮功能和 nNOS 表达来减轻糖尿病相关的阴茎血流动力学损伤。 ICA II可以改变糖尿病大鼠海绵体纤维肌肉病理结构，该结构可能受到TGFβ1/Smad2/CTGF和NO-cGMP信号通路的调节。
Icariin and icariside II (ICA II), 2 active components isolated from herba epimedii, have a closely structural relationship. There is evidence that icariin may be useful in the treatment of erectile dysfunction (ED); however, the study on the therapeutic efficacy of ICA II on ED is currently scant. We investigated the effects of ICA II on improving erectile function of rats with streptozocin-induced diabetes. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into normal control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 4 groups including a saline-treated placebo arm and 3 ICA II treated models (1, 5, and 10 mg/kg/d). After 3 months, penile hemodynamics was measured by cavernous nerve electrostimulation (CNE) with real time intracorporal pressure assessment. Penises were harvested with subsequent histological examination (picrosirius red stain, Hart elastin stain, and immunohistochemical stain) and Western blots to explore the expression of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and transforming growth factor beta 1 (TGF beta 1)/Smad2 signaling pathways. Diabetes significantly attenuated erectile responses to CNE. Diabetic rats had decreased corpus cavernosum smooth muscle/collagen ratio and endothelial cell content relative to the control group. The ratio of collagen I to III was significantly lower in the corpora of diabetic rats; furthermore, cavernous elastic fibers were fragmented in the diabetic animals. Neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase, and vascular endothelial growth factor were expressed at lower levels in the diabetic group; ICA II-treated diabetic rats had higher expression in the penis relative to placebo-treated diabetic animals. Both the TGF beta 1/Smad2/connective tissue growth factor (CTGF) signaling pathway and apoptosis were down-regulated in the penis from ICA II-treated rats. ICA II treatment attenuates diabetes-related impairment of penile hemodynamics, likely by increasing smooth muscle, endothelial function, and nNOS expression. ICA II could alter corpus cavernosum fibrous-muscular pathological structure in diabetic rats, which could be regulated by the TGF beta 1/Smad2/CTGF and NO-cGMP signaling pathways.