Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction

Ding WANG; Shaofeng ZHANG; Xue JIANG; Xiang LYU; Taiping ZHU; Jiakun LIN

doi:10.13422/j.cnki.syfjx.20221892

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Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction

更新时间：2022-08-11

- Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 18, Pages: 77-84(2022)
- 作者机构：
  
  1.石家庄医学高等专科学校，石家庄 050000
  2.柏乡县中心医院，河北邢台 055450
  3.江西萍乡市中医院，江西萍乡 337000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221892
  CLC： R285.5;R966;R587.1;R698
- Published：20 September 2022，
  
  Published Online：23 March 2022，
  
  Received：14 September 2021，
- 稿件说明：
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王丁,张韶峰,姜雪等.益元起痿丸治疗糖尿病性勃起功能障碍大鼠作用机制[J].中国实验方剂学杂志,2022,28(18):77-84.

WANG Ding,ZHANG Shaofeng,JIANG Xue,et al.Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):77-84.
王丁,张韶峰,姜雪等.益元起痿丸治疗糖尿病性勃起功能障碍大鼠作用机制[J].中国实验方剂学杂志,2022,28(18):77-84. DOI： 10.13422/j.cnki.syfjx.20221892.

WANG Ding,ZHANG Shaofeng,JIANG Xue,et al.Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):77-84. DOI： 10.13422/j.cnki.syfjx.20221892.

摘要

目的

观察益元起痿丸对糖尿病性勃起功能障碍（DMED）大鼠的治疗作用，并探讨其对一氧化氮（NO）/环磷酸鸟苷（cGMP）信号通路的调控作用。

方法

55只2~3月龄清洁级、健康SD雄鼠腹腔注射链脲佐菌素（STZ）建立DMED大鼠模型，另取10只2~3月龄清洁级、健康SD雄鼠记为正常组；建模成功后随机分组，西地那非组予以西地那非5 mg·kg

-1

灌胃，益元起痿丸低、中、高剂量组予以1.5、3.0、6.0 g·kg

-1

益元起痿丸灌胃，模型组与正常组均予以生理盐水灌胃，各10 mL·kg

-1

，每天1次，共2个月。干预后，采用压力检测系统测定各组大鼠的阴茎勃起功能；苏木素-伊红（HE）染色观察阴茎海绵体病理变化，透射电镜观察大鼠阴茎海绵体超微结构；硝酸还原酶法检测阴茎海绵体组织NO水平，酶联免疫吸附测定法（ELISA）检测cGMP及晚期糖基化总产物（AGEs）水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠阴茎组织内皮型一氧化氮合成酶（eNOS）、神经源型一氧化氮氧合酶（nNOS）、总一氧化氮氧合酶（NOS）、5型磷酸二酯酶（PDE5）信使核糖核酸（mRNA）表达；蛋白免疫印迹法（Western blot）检测上述蛋白表达。

结果

与正常组比较，模型组大鼠阴茎海绵窦内压（ICP），阴茎海绵体组织NO、cGMP含量及nNOS、NOS mRNA和蛋白表达均降低，PDE5 mRNA和蛋白表达均升高，上述差异均有统计学意义（

0.05）；与模型组比较，西地那非组、益元起痿丸低、中、高剂量组ICP，阴茎海绵体组织NO、cGMP含量及nNOS、NOS mRNA和蛋白表达均升高，PDE5 mRNA和蛋白表达均降低（

0.05）。正常组阴茎海绵体组织及细胞超微结构均未见病理改变，模型组有严重病理改变，西地那非组、益元起痿丸各剂量组均较模型组改善，且益元起痿丸高剂量组病理改变更轻更佳。

结论

益元起痿丸可以改善DMED大鼠阴茎勃起功能，减轻阴茎海绵体病理损伤，作用机制可能与促进nNOS、NOS表达，抑制PDE5表达，激活NO/cGMP信号通路有关。

Abstract

Objective

To observe the therapeutic effect of Yiyuan Qiwei pills （YYQW） on diabetes mellitus-induced induced erectile dysfunction （DMED） in rats and explore its regulation on the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） signaling pathway.

Method

Fifty-five healthy SD male rats of clean grade aged 2-3 months underwent intraperitoneal injection of streptozotocin （STZ） to induce the DMED model， and another 10 healthy SD male rats of clean grade aged 2-3 months were assigned to the control group. The model rats were randomly divided into a model group， a sildenafil group （5 mg·kg

-1

，

）， and low-， medium-， and high-dose YYQW groups （1.5， 3.0， 6.0 g·kg

-1

，

）. The rats in the model group and the control group were given normal saline by gavage at 10 mL·kg

-1

， once a day for two months. After intervention， the penile erectile function of rats in each group was measured by a pressure detection system. The pathological changes and ultrastructure of penile corpus cavernosum were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. The level of NO in the corpus cavernosum was detected by nitrate reductase. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cGMP and advanced glycation end products （AGEs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of endothelial nitric oxide synthase （eNOS）， neurogenic nitric oxide synthase （nNOS）， total nitric oxide synthase （NOS）， and phosphodiesterase type5 （PDE5） in rat penile tissues. The expression of above proteins was detected by Western blot.

Result

Compared with the control group， the model group showed decreased intracavernous pressure （ICP）， NO， and cGMP levels， reduced mRNA and protein expression of nNOS and NOS， and increased PDE5 mRNA and protein expression （

0.05）. Compared with the model group， the sildenafil group and the YYQW groups displayed increased ICP， NO， and cGMP levels， elevated mRNA and protein expression levels of nNOS and NOS， and reduced PDE5 mRNA and protein expression levels （

0.05）. There were no pathological changes in the tissues and cell ultrastructure of the corpus cavernosum in the control group， while serious pathological changes were observed in the model group. Additionally， the sildenafil group and the YYQW groups were superior to the model group， the optimal effect was observed in the high-dose YYQW group.

Conclusion

YYQW can improve the penile erectile function of DMED rats and reduce the pathological damage of corpus cavernosum. The mechanism may be related to the promotion of nNOS and NOS expression， the inhibition of PDE5 expression， and the activation of the NO/cGMP signaling pathway.

关键词

益元起痿丸糖尿病性勃起功能障碍一氧化氮环磷酸鸟苷一氧化氮氧合酶5型磷酸二酯酶

Keywords

Yiyuan Qiwei pillsdiabetes mellitus induced erectile dysfunctionnitric oxidecyclic guanosine monophosphatenitric oxide synthasephosphodiesterase type5

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