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Asian Journal of Andrology 2003年第2期 130-130页

作者： Jian-Li CHENG, Li-Quan HUDepartment of Urology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China

Objective: To investigate the alterations in nNOS containing nerve fibers in corpus cavernosum of spontaneous hypertension rats (SHR). Methods: Twelve male SHR and 12 male WKY rats, both aged 6 weeks, were separately divided into 4- and 12-week observation groups at random. At the end of the observation period, the erectile function was assessed and the number of cavernosal nNOS containing nerve fibers determined. Results: Significant differences existed in the erection frequency and the number of nNOS containing nerve fibers between the SHR rats and the WKY controls (P< 0.01); there was also a significant difference in the numbers of nNOS containing nerve fibers between the SHR 4- and 12-week observation groups (P<0.05). Conclusion: The erectile function and the number of nNOS containing nerve fibers were significantly reduced in SHR rats. The decrease in nNOS containing nerve fibers may be one of the mechanisms underlying erectile dysfunction in hypertensive rats.

关键词： nNOS erectile dysfunction hypertension corpus cavernosum rats

Relaxation mechanisms of cavernosum tissue in vitro neferine on the rabbit corpus

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Asian Journal of Andrology 2007年第6期9卷 795-800页

作者： Jun Chen Jun Qi Fang Chen Ji-Hong Liu Tao Wang Jun Yang Chun-Ping Yin Department of Urology Xinhua Hospital School of Medicine Shanghai Jiaotong University Shanghai 200092 China Department of Urology 3Department of Pharmacy Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Aim： To investigate the relaxation mechanisms of neferine （Nef） on the rabbit corpus cavemosum tissue in vitro. Methods： Strips of rabbit corpus cavemosum were mounted in organ chambers. The effects of Nef were examined on isolated muscle strips precontracted with phenylephrine （PE） alone, in the presence of NW-nitro-L-arginine （LNNA, a nitric oxide synthase inhibitor）, 1-H-[ 1,2,4]oxadiazolo[4,3-tx]quinoxalin- 1-one （ODQ, a guanylyl cyclase inhibitor）, indomethacin （cyclooxygenase inhibitor）, tetraethylammonium （Ca^2＋ -activated K^＋ channel blocker）, 4-aminopiridine （4-AP ,voltage dependent K^＋ channel blocker） and glibenclamide （ATP sensitive K^＋channel blocker）. The effects of Nef on KCl-induced contraction of isolated muscle strips were also investigated. The procedure of calcium absencecalcium addition was designed to observe the effect of Nef on two components of the contractile responses to PE based on the source of Ca^2＋（extracellular vs. intracellular）. Results： corpus cavemosum strips relaxed in response to Nef （10-9-10-4 mol/L） in a concentration-dependent manner with an IC50 of 4.60 × 10^-6 mol/L. However, they were not affected by LNNA, ODQ, indomethacin or K^＋-channel blockers. Nef （10^-6 mol/L, 10^-5 mol/L） concentration dependently reduced the maximal contraction response of isolated strips induced by KC1 to 79.3% ± 5.5% and 61.5% ±3.2%, respectively （P 〈 0.01）. In the calcium absence-calcium addition procedure, Nef 10.5 mol/L inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE （2 × 10^5 mol/L）（P 〈 0.05）. The inhibition ratios were 26.2% ± 5.4% and 48.3% ±7.6%, respectively. Conclusion： The results of the present study suggest that Nef possesses a relaxant effect on rabbit corpus cavemosum tissues, which is attributable to the inhibition of extracellular Ca^2＋ influx and the inhibition of release of intracellular stored Ca^2＋, but not mediated by the release of nitric oxide, prostaglandins or

关键词： neferine corpus cavernosum relaxation

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold

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Asian Journal of Andrology 2024年第3期26卷 260-267页

作者： Yu-Zhuo Chen Yi-Hong Zhou Min-Bo Yan Ming Xiao Biao Liu Ying-Hao Yin Xiao-Li Tan Yong-Quan Huang Yu-Hong Lin Ting Xie Jia-Li Tian Qi Wang Jian-Ying Li Zi-Zhou Meng Zheng Li Emily Xing Yu-Xin Tang Ya-Wei Li Zhong-Zhen Su Liang-Yu Zhao Department of Ultrasound The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Interventional Medicine Guangdong Provincial Key Laboratory of Biomedical ImagingThe Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Urology The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Andrology the Center for Men’s HealthUrologic Medical CenterShanghai Key Laboratory of ReproductiveMedicineShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Cedars-Sinai Medical Center Los AngelesCA 90024USA

Ex vivo tissue culture of the human corpus cavernosum(cc)can be used to explore the tissue structural changes and complex signaling *** present,artificial Cc-like tissues based on acellular or three-dimensional(3D)-printed scaffolds are used to solve the scarcity of primary penis tissue ***,inconvenience and high costs limit the wide application of such ***,we describe a simple,fast,and economical method of constructing artificial CC-like *** Cc fibroblasts(FBs),endothelial cells(ECs),and smooth muscle cells(SMCs)were expanded in vitro and mixed with Matrigel in specific proportions.A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing,creating a porous,spongy,and spatial *** Cc FBs produced a variety of signaling factors,showed multidirectional differentiation potential,and grew in a 3D grid in Matrigel,which is necessary for CC-like tissue to maintain a porous structure as a cell *** the C-like tissue,ECs covered the surface of the lumen,and SMCs were located inside the trabeculae,similar to the structure of the primary *** cell components remained stable for 3 days in vitro,but the EC content decreased on the 7th ***/integrated(WNT)signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue,inducing the same changes in characteristics as in the primary *** study describes a preparation method for human artificial cC-like tissue that may provide an improved experimental platform for exploring the function and structure of the cC and conducting drug screening for erectile dysfunction therapy.

关键词： artificial tissue corpus cavernosum ex vivo fibroblasts

Physiological significance of nitrergic transmission in human penile erection

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Asian Journal of Andrology 2000年第1期2卷 51-56页

作者： P.G.Adaikan S.C.Ng Department of Obstetrics & Gynaecology National University Hospital National University of Singapore Lower Kent Ridge Road Singapore 119 074Department of Obstetrics & Gynaecology National University Hospital National University of Singapore Lower Kent Ridge Road Singapore 119 074

Aim: Epididymal proteins are known to play an important role in the maturation of spermatozoa, we ought to deter-mine if there are regional differences in androgen-dependent epididymal proteins. Methods: A group of adult rats wascastrated and epididymides were removed three days following castration. The epididymides were dissected into caput,corpus and cauda segments, homogenized, and proteins were fractionated by anion exchange HPLC. Proteins in select-ed fractions were resolved by SDS-PAGE and visualized by silver staining. Results: It was observed that the levels ofmultiple proteins drastically reduced in the various regions of epididymis of the orchiectomized rats. Conclusion: Theepididymal proteins appear to be useful markers to study androgenic action in the epididymis.

关键词： erection neurotransmission corpus cavernosum nitric oxide cyclic GMP

Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

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Asian Journal of Andrology 2012年第4期14卷 635-642页

作者： Ines Tomada Nuno Tomada Henrique Almeida Delminda Neves Department of Experimental Biology Faculty of MedicineUniversidade do Porto--Alameda ProfHernmai MonteiroPorto 4200-319Portugal Instituto de Biologia Molecular e Celular(IBMC) Universidade do Porto--Rua do Campo Alegre 823Porto 4150-180Portugal Department of Urology Centro Hospital S.JoaoEPE-Alameda ProfessorHernmani MonteiroPorto 4200-319Portugal

The purpose of the current study was to evaluate the effect of a high-fat （HF） diet, energy restriction and exercise on the expression of vascular endothelial growth factor （VEGF）, angiopoietin （Ang） I and 2, and their receptors in rat corpus cavernosum （CC）. Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays （VEGF, VEGF receptor （VEGFR） I and 2, Angl, Ang2 and Tie2） and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase （eNOS） and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol （HDL-c） levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.

关键词： angiopoietins corpus cavernosum endothelial dysfunction energy restriction exercise high-fat diet VEGF

Upregulation of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis by a combination of Yinyanghuo(Herba Epimedii Brevicornus) and Cheqianzi(Semen Plantaginis) improves erectile function in spontaneously hypertensive rats

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Journal of Traditional Chinese Medicine 2020年第5期40卷 836-844页

作者： Zhang Hongguan Liu Yude Rao Lian Cen Yanyou Cheng Kaili Guangzhou University of Chinese Medicine Guangzhou 510405China partment of cardiovascularmedicine the First Affiliated Hospital of Guangzhou Universityof Chinese MedicineGuangzhou 510405China

OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats(SHRs),and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor(ACE2/Ang[1-7]/Mas receptor)axis in this ***:A total of 24 SHRs were randomly assigned to three groups:SHR-control,low-dose(12.5 g/kg)and high-dose(25 g/kg)HEB+SP(HEBSP).Eight Wistar-Kyoto rats were used as normal *** was administered by oral gavage for 28 *** function was measured once a week using the Heaton *** 4 weeks of treatment,the corpus cavernosum was harvested from each rat to measure nitric oxide(NO),nitric oxide synthase(e NOS)and Ang(1-7)levels,as well as ACE2,Mas receptor and neuronal nitric oxide synthase(n NOS)protein ***:After 4 weeks of treatment,HEBSP significantly increased erectile function in the treated group compared with SHR-control group(P<0.01).Additionally,HEBSP treatment significantly increased cavernosal levels of Ang(1-7),e NOS and ***,HEBSP significantly elevated the expression levels of ACE2,Mas receptor and n *** beneficial effects were elevated in the high-dose HEBSP ***:HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang(1-7)/Mas receptor axis,e NOS and n NOS pathways.

关键词： Rats,Inbred SHR Peptidyl-Dipeptidase A Angiotensins Nitric oxide synthase corpus cavernosum Yinyanghuo(Herba Epimedii Brevicornus) Cheqianzi(Semen Plantaginis)

Recent insights into androgen action on the anatomical and physiological substrate of penile erection

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Asian Journal of Andrology 2006年第1期8卷 3-9页

作者： Louis J.G.Gooren Farid Saad Department of Endocrinology Andrology SectionVrije Universiteit Medical Center1007 MB AmsterdamThe Netherlands Gulf Medical College Medical University of theUnited Arab Emirates2563 Ajman UAE Andrology DepartmentSchering AG13342 BerlinGermany

Erectile response is centrally and peripherally regulated by androgens. The original insights into the mechanisms of action of androgens were that androgens particularly exert effects on libido and that erections in response to erotic stimuli were relatively androgen-independent. It was shown that sexual functions in men required androgen levels at the low end of reference values of testosterone. So it seemed that testosterone was not useful treatment for men with erectile difficulties, particularly following the advent of the phosphodiesterase type 5 （PDE5） inhibitors. However, approximately 50% of those treated with PDE5 inhibitors discontinue their treatment. A number of recent developments shed new light on testosterone treatment of erectile dysfunction （ED） in aging men. （1） A recent insight is that, in contrast to younger men, elderly men might require higher levels of testosterone for normal sexual functioning. （2） Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men, and that testosterone improves the therapeutical response to PDE5 inhibitors considerably. （3） There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, reversible upon androgen replacement. The synthesis of PDE5 is upregulated by androgens, and the arterial inflow into the penis is improved by giving androgen. The above invites a re-examination of the merits of giving testosterone to aging men with ED. The beneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment. （Asian J Androl 2006 Jan; 8： 3-9）

关键词： testosterone erection corpus cavernosum phosphodiesterase type 5 inhibitors

Effect of androgen deprivation on penile ultrastructure

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Asian Journal of Andrology 2003年第1期5卷 33-36页

作者： Zhou-JunSHEN Xie-LaiZHOU Ying-LiLU Zhao-DianCHEN DepartmentofUrology FirstAffiliatedHospital DepartmentofEndocrinology SirRunRunShawHospitalSchoolofMedicineZhejiangUniversityHangzhou310003China

Aim: To investigate the ultrastructural changes of penile corpus cavernosum and tunica albuginea in rats treated with castration or finasteride. Methods: Eighteen male Sprague-Dawley rats of nine weeks old were randomly divided into three groups with 6 rats each. Group A served as the control, Group B was castrated and Group C, treated with finasteride. Four weeks later, rats were anesthetized and blood samples obtained for the determination of serum testosterone (T) and dihydrotestosterone (DHT) levels; penile tissues were taken for scanning electron microscopy. Results: The T, free T and DHT levels in Group B and the DHT level in Group C were significantly lower than those in Group A (P0.05). Elastic fibers in the tunica albuginea of Group A were very rich and arranged regularly and undulatedly, but in Group B, most of the elastic fibers were replaced by collagenous fibers. In Group C, the tunica albuginea was mainly composed of thick and irregular-arranged collagenous fibers. In Group A, there were abundant smooth muscle fibers in the trabeculae of corpus cavernosum, but they were much less in Group C and scarce or even disappeared in Group B. In Groups B and C, the diminished/disappeared smooth muscle fibers were replaced by irregularly arranged collagenous fibers. Conclusion: In rats, androgen is essential for maintaining the normal structure of penile tunica albuginea and corpus carvenosum.

关键词： corpus cavernosum tunica albuginea androgens penis scanning electron microscopy

Effects of Korean ginseng berry extract （GB0710） on penile erection： evidence from in vitro and in vivo studies

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Asian Journal of Andrology 2013年第4期15卷 503-507,I0008页

作者： Kang Su Cho Chan Woong Park Chun-Ki Kimt Hee Young Jeon Wan Gi Kim Sang Jun Lee Young-Myeong Kim Joo Yong Lee Young Deuk Choi Department of Urology Severance Hospital Urological Science Institute Yonsei University College of Medicine Seou1120-752 Korea R&D Center Amorepacific Corporation Yongin Gyeonggi-do 446-729 Korea Vascular System Research Center and Department of Molecular and Cellular Biochemistry School of Medicine Kangwon National University Chunchon 200-701 Korea and Clinical Trial Center for Medical Devices Yonsei University College of Medicine Seoul 120-752 Korea

Several reports have promoted the root-derived Korean red ginseng （KRG; Panax ginseng） as alternative treatment for erectile dysfunction （ED）, and ginsenosides are known to be the principal active ingredients of ginseng. Recent studies showed that ginseng berries produce more ginsenosides than KRG; thus, we investigated the ability of the Korean ginseng berry extract GB0710 to relax the penile corpus cavernosum smooth muscle （CCSM） in this study. As a comparative control, the results were compared to those obtained using KRG. In addition, possible mechanisms of action for GB0710 were investigated. While KRG and GB0710 both displayed dose-dependent relaxation effects on precontracted rabbit CCSM in vitro, GB0710 was shown to be more potent than KRG. The GBO710-induced relaxation could be partially reduced by removing the endothelium. In addition, pre-treatment with several nitric oxide （NO） inhibitors significantly inhibited the relaxation of muscle strips. Furthermore, administration of GB0710 increased intracavernosal pressure （ICP） in a rat in vivo model in both a dose- and duration-dependent manner. Intracellular NO production in human microvascular endothelial cells could be induced by GB0710 and inhibited by NG-monomethyI-L-arginine. In conclusion, GB0710 had a greater relaxation effect on rabbit CCSM than did KRG extract, and increased ICP in a rat model in both a dose- and a duration-dependent manner. This relaxine effect might be mediated bv NO production.

关键词： corpus cavernosum erectile dysfunction (ED) ginseng berry nitric oxide (NO) smooth muscle