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在链脲佐菌素诱导的糖尿病大鼠模型中,脂肪来源干细胞分泌的外泌体通过递送 corin 蛋白来预防高糖诱导的勃起功能障碍。

Exosomes from adipose-derived stem cells protect against high glucose-induced erectile dysfunction by delivery of corin in a streptozotocin-induced diabetic rat model.

作者信息

Wang Jian, Mi Yuanyuan, Wu Sheng, You Xiaoming, Huang Yi, Zhu Jin, Zhu Lijie

机构信息

Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214041, China.

Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.

出版信息

Regen Ther. 2020 May 15;14:227-233. doi: 10.1016/j.reth.2020.03.002. eCollection 2020 Jun.

Abstract

INTRODUCTION

Increasing study have found that stem cell transplantation have a therapeutical effect to diabetes mellitus (DM)-induced erectile dysfunction (ED). So, the aim of this study was to evaluate the beneficial effect of corin from adipose-derived stem cells (ADSCs) on DM-induced ED.

METHODS

Exosomes were isolated from ADSCs (ADSC-EXOs) or from ADSCs in which corin gene expression was silenced by siRNA (siCorin). For studies, rats with streptozotocin-induced DM were intravenously injected with ADSC-EXOs or siCorin-ADSC-EXOs. Two weeks later, intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured to assess erectile function, and penile tissues were harvested for further evaluation of levels of inflammatory factors and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and neuronal nitric oxide synthase (nNOS). We also evaluated the recovery of neurovascular function in penile tissues by immunofluorescence analysis.

RESULTS

The results showed that ADSC-EXOs restored erectile function in diabetic rats, as determined by the ICP/MAP ratio. Exosomes from ADSCs also promoted neurovascular function and suppressed expression of inflammatory factors. In contrast, the decreased content of corin in exosomes after silencing corin in ADSCs reduced the therapeutic effect of exosomes on ED.

CONCLUSION

These findings demonstrated the therapeutic mechanism underlying the use of ADSC-EXOs for treating ED and the beneficial effect of corin.

摘要

引言

越来越多的研究发现,干细胞移植对糖尿病(DM)所致勃起功能障碍(ED)具有治疗作用。因此,本研究旨在评估脂肪来源干细胞(ADSCs)中的corin对DM所致ED的有益作用。

方法

从ADSCs中分离出外泌体(ADSC-EXOs),或从通过小干扰RNA(siRNA)使corin基因表达沉默的ADSCs中分离出外泌体(siCorin)。在研究中,将链脲佐菌素诱导的DM大鼠静脉注射ADSC-EXOs或siCorin-ADSC-EXOs。两周后,测量海绵体内压(ICP)和平均动脉压(MAP)以评估勃起功能,并采集阴茎组织以进一步评估炎症因子水平以及心房钠尿肽(ANP)、脑钠尿肽(BNP)和神经元型一氧化氮合酶(nNOS)的表达。我们还通过免疫荧光分析评估了阴茎组织中神经血管功能的恢复情况。

结果

结果显示,通过ICP/MAP比值测定,ADSC-EXOs恢复了糖尿病大鼠的勃起功能。ADSCs来源的外泌体还促进了神经血管功能并抑制了炎症因子的表达。相比之下,ADSCs中corin沉默后外泌体中corin含量的降低降低了外泌体对ED的治疗效果。

结论

这些发现证明了使用ADSC-EXOs治疗ED的潜在治疗机制以及corin的有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d66/7229419/4da4290f1d02/gr1.jpg

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