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人参皂苷Rg3改善链脲佐菌素诱导的糖尿病大鼠的勃起功能。

Ginsenoside Rg3 improves erectile function in streptozotocin-induced diabetic rats.

作者信息

Liu Tao, Peng Yi-Feng, Jia Chao, Yang Ben-Hai, Tao Xia, Li Jing, Fang Xiang

机构信息

Department of Sexual Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China.

出版信息

J Sex Med. 2015 Mar;12(3):611-20. doi: 10.1111/jsm.12779. Epub 2014 Dec 1.

Abstract

INTRODUCTION

Ginsenoside Rg3 is one of the active ingredients isolated from Panax ginseng C.A. Meyer. Previous studies demonstrated that Rg3 has antioxidant and neuroprotective abilities.

AIM

The purpose of this study was to evaluate the protective effect of Rg3 on erectile function in streptozotocin (STZ)-induced diabetic rats.

METHODS

Two-month-old Sprague-Dawley male rats received a one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16-hour fast. Three days later, rats were randomly divided into four groups and were treated with daily gavage feedings of a mix of distilled saline water and 0.5% carboxymethylcellulose or Rg3 dissolved in the mix at doses of 10 mg/kg and 100 mg/kg for 3 months. A sham group underwent IP injection of saline followed by daily gavage of the above mix for 3 months.

MAIN OUTCOME MEASURE

Erectile function was assessed by cavernosal nerve electrostimulation at 3 months. The penis was then harvested and deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. Western blot was performed to examine cleaved caspase-3, platelet endothelial cell adhesion molecule (PECAM)-1, and smooth muscle actin (SMA). Neural regeneration was measured by nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry.

RESULTS

In the negative control group, the functional evaluation showed a lower mean intracavernosal pressure (ICP) with cavernosal nerve stimulation than in the sham group; there was a significant change in the expression of cleaved caspase-3, bcl-2, bcl-xl, PECAM-1, and SMA, as well as in the SOD and MDA production in the corpus cavernosum. Histological analysis of specimens stained for NADPH showed a significant change in the staining quality of the neurons in the dorsal nerves; TUNEL showed a greater apoptotic index in corpus cavernosum cells. With daily oral gavage with 100 mg/kg Rg3, the ICP/mean arterial pressure value was significantly higher than in the controls. The level of cleaved caspase-3, bcl-2, bcl-xl, PECAM-1, and SMA and the number of positively stained nerve fibers tended to revert to normal after Rg3 treatment. The apoptotic index in corpus cavernosum cells was lowered.

CONCLUSION

Oral gavage with Rg3 appears to both prevent degeneration of neurons in the dorsal nerves and exert an antioxidant effect in the corpus cavernosum of rats.

摘要

引言

人参皂苷Rg3是从人参(C.A. Meyer)中分离出的活性成分之一。先前的研究表明,Rg3具有抗氧化和神经保护能力。

目的

本研究旨在评估Rg3对链脲佐菌素(STZ)诱导的糖尿病大鼠勃起功能的保护作用。

方法

2月龄的Sprague-Dawley雄性大鼠在禁食16小时后接受一次腹腔注射(IP)STZ(60 mg/kg)或溶剂注射。三天后,大鼠被随机分为四组,每天用蒸馏水和0.5%羧甲基纤维素的混合物或溶解在该混合物中的Rg3(剂量分别为10 mg/kg和100 mg/kg)进行灌胃,持续3个月。假手术组接受腹腔注射生理盐水,随后每天用上述混合物进行灌胃,持续3个月。

主要观察指标

3个月时通过海绵体神经电刺激评估勃起功能。然后摘取阴茎并进行脱氧核苷酸末端转移酶dUTP缺口末端标记(TUNEL)检测。进行蛋白质免疫印迹法检测裂解的半胱天冬酶-3、血小板内皮细胞黏附分子(PECAM)-1和平滑肌肌动蛋白(SMA)。通过烟酰胺腺嘌呤二核苷酸磷酸(NADPH)-黄递酶染色测量神经再生。通过比色法检测超氧化物歧化酶(SOD)和丙二醛(MDA)水平。

结果

在阴性对照组中,功能评估显示海绵体神经刺激后的平均海绵体内压(ICP)低于假手术组;裂解的半胱天冬酶-3、bcl-2、bcl-xl、PECAM-1和SMA的表达以及海绵体中SOD和MDA的产生有显著变化。对NADPH染色的标本进行组织学分析显示,背神经中神经元的染色质量有显著变化;TUNEL检测显示海绵体细胞的凋亡指数更高。每天口服100 mg/kg Rg3后,ICP/平均动脉压值显著高于对照组。Rg3治疗后,裂解的半胱天冬酶-3、bcl-2、bcl-xl、PECAM-1和SMA的水平以及阳性染色神经纤维的数量趋于恢复正常。海绵体细胞的凋亡指数降低。

结论

口服Rg3似乎既能预防背神经中神经元的退化,又能在大鼠海绵体中发挥抗氧化作用。

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