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姜黄素给药通过激活雄激素受体促进水通道蛋白8表达,减轻1型糖尿病大鼠的精囊损伤。

Curcumin administration alleviates seminal vesicle damage in type 1 diabetic rats by promoting AQP8 expression through AR activation.

作者信息

Ni Dawei, Liu Kun, Wu Ning, You Bin, Yang Baibing, Wu Wei, Dai Yutian

机构信息

Department of urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China.

Department of andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Sci Rep. 2025 Jan 30;15(1):3804. doi: 10.1038/s41598-024-74750-5.

Abstract

Diabetes is a detriment to male reproductive health, notably through its capacity to diminish secretion from accessory glands such as the seminal vesicles and prostate, which are crucial for reproductive function. Curcumin, a naturally derived polyphenol renowned for its anti-inflammatory and antioxidative attributes, has demonstrated potential in mitigating tissue damage across various organs in diabetic patients. Despite its established benefits, the specific impact of curcumin on seminal vesicle damage in the context of diabetes remains underexplored. This investigation delves into the therapeutic potential of curcumin in ameliorating seminal vesicle damage in diabetic rats, thereby elucidating its underlying mechanisms. This study focused on twenty male SD rats divided into two distinct groups, a control cohort and a diabetic contingent, and employed a streptozocin (STZ)-induced type 1 diabetic rat model to ascertain seminal vesicle alterations secondary to diabetes. Ultrasonography was used to measure rat seminal vesicle sizes for comparison with postdissection measurements. This study revealed that (1) seminal vesicle volume and seminal fluid secretion were reduced in diabetic rats and (2) ultrasonography can predict seminal vesicle secretory dysfunction in diabetic rats, providing a theoretical basis for selecting animal models of diabetic seminal vesicle dysfunction for subsequent studies. Thirty male SD rats were subsequently divided into three groups: control, diabetic, and curcumin-treated. The curcumin group, which was subjected to a one-month-long intervention after STZ-induced diabetes onset, exhibited significant histological and functional recovery. Haematoxylin‒eosin (HE) staining revealed disordered seminal vesicle tissue structures and decreased epithelial cell height in diabetic rats, which was partially restored after curcumin treatment. Western blot and PCR results demonstrated that the expression levels of androgen receptor (AR) and aquaporin (AQP)8 in the seminal vesicle tissues of diabetic rats were decreased, whereas curcumin treatment led to increases in the expression levels of AR and AQP8. Seminal vesicle cells were cultured in vitro and divided into six groups: control, HG, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM. After 48 h of intervention, the fructose concentration in the culture medium was measured, and the expression of AR and AQP8 in the control, HG, and HG-CUR-20 µM groups was determined via Western blotting and PCR. The results revealed that the expression of AR and APQ8 in high glucose-treated seminal vesicle cells was decreased and that curcumin treatment upregulated the expression of AR and AQP8. After the addition of bicalutamide (an AR inhibitor), the expression of AQP8 was reduced. These findings suggest that curcumin may alleviate seminal vesicle damage in type 1 diabetic rats by activating the AR-AQP8 pathway.

摘要

糖尿病对男性生殖健康有害,尤其是通过其减少附属腺体(如精囊和前列腺)分泌的能力,而这些附属腺体对生殖功能至关重要。姜黄素是一种天然衍生的多酚,以其抗炎和抗氧化特性而闻名,已显示出减轻糖尿病患者各器官组织损伤的潜力。尽管其益处已得到证实,但姜黄素在糖尿病背景下对精囊损伤的具体影响仍未得到充分研究。本研究探讨姜黄素改善糖尿病大鼠精囊损伤的治疗潜力,从而阐明其潜在机制。本研究聚焦于20只雄性SD大鼠,分为两个不同的组,即对照组和糖尿病组,并采用链脲佐菌素(STZ)诱导的1型糖尿病大鼠模型来确定糖尿病继发的精囊改变。使用超声测量大鼠精囊大小,并与解剖后的测量结果进行比较。本研究表明:(1)糖尿病大鼠的精囊体积和精液分泌减少;(2)超声可预测糖尿病大鼠的精囊分泌功能障碍,为后续研究选择糖尿病性精囊功能障碍动物模型提供了理论依据。随后,将30只雄性SD大鼠分为三组:对照组、糖尿病组和姜黄素治疗组。姜黄素组在STZ诱导的糖尿病发病后进行了为期一个月的干预,显示出显著的组织学和功能恢复。苏木精-伊红(HE)染色显示糖尿病大鼠精囊组织结构紊乱,上皮细胞高度降低,姜黄素治疗后部分恢复。蛋白质印迹和PCR结果表明,糖尿病大鼠精囊组织中雄激素受体(AR)和水通道蛋白(AQP)8的表达水平降低,而姜黄素治疗导致AR和AQP8表达水平升高。体外培养精囊细胞并分为六组:对照组、高糖组、5μM姜黄素高糖组、10μM姜黄素高糖组、20μM姜黄素高糖组和50μM姜黄素高糖组。干预48小时后,测量培养基中的果糖浓度,并通过蛋白质印迹和PCR测定对照组、高糖组和20μM姜黄素高糖组中AR和AQP8的表达。结果显示,高糖处理的精囊细胞中AR和APQ8的表达降低,姜黄素处理上调了AR和AQP8的表达。加入比卡鲁胺(一种AR抑制剂)后,AQP8的表达降低。这些发现表明,姜黄素可能通过激活AR-AQP8途径减轻1型糖尿病大鼠的精囊损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b18/11782618/54dd3587caf5/41598_2024_74750_Fig1_HTML.jpg

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