Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Life Sci. 2018 Oct 15;211:63-73. doi: 10.1016/j.lfs.2018.09.019. Epub 2018 Sep 8.
As nitric oxide (NO) production is essential for insulin signaling, glucose uptake, endothelial function, and regulation of apoptosis, the loss of bioavailable NO may be a mechanism underlying the development of diabetes complication. Dietary nitrate acts as a substrate for NO generation, thus serving as a physiological source of NO. This study evaluated the therapeutic effects of nitrate supplementation on the apoptosis-induced testicular disorders in diabetic rats.
Fifty male Wistar rats were divided into five groups; control, control with 100 mg/L nitrate in distilled drinking water, diabetes, diabetes treated with 2-4 U/day NPH insulin, diabetes treated with 100 mg/L nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and epididymis were collected to assess the apoptosis process and the stereology of testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose, insulin, and NOx levels were investigated.
The results of this study indicated that nitrate treatment ameliorated the sperm parameters, testicular morphometrical and stereological alterations, reduced blood glucose, the number of TUNEL positive cells and tubules, and testicular expressions of p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and NOx levels, and testicular expression of miR-449a in streptozotocin-induced diabetic rats.
Our in vivo evidence revealed that nitrate treatment may has a favorable effect as an exogenous NO donor on experimental diabetic testicular damages in which NO bioavailability is impaired.
由于一氧化氮（NO）的产生对于胰岛素信号转导、葡萄糖摄取、内皮功能和细胞凋亡的调节至关重要，因此生物可利用的 NO 的丧失可能是糖尿病并发症发展的一种机制。膳食硝酸盐可作为 NO 生成的底物，因此是 NO 的生理来源。本研究评估了硝酸盐补充对糖尿病大鼠诱导的睾丸组织细胞凋亡的治疗作用。
将 50 只雄性 Wistar 大鼠分为五组：对照组、对照组给予蒸馏饮用水中 100mg/L 硝酸盐、糖尿病组、糖尿病组给予 2-4U/天 NPH 胰岛素、糖尿病组给予蒸馏饮用水中 100mg/L 硝酸盐。8 周后，采集血样、睾丸和附睾，评估凋亡过程和睾丸组织的体视学、精子运动、形态和 DNA 片段化，以及 miR-449a、p53、Pdcd4 和 Pacs2mRNA 的 mRNA 表达，以及血清葡萄糖、胰岛素和 NOx 水平。
本研究结果表明，硝酸盐治疗可改善精子参数、睾丸形态学和体视学改变、降低血糖、TUNEL 阳性细胞和小管数量以及睾丸中 p53、Pdcd4 和 Pacs2mRNA 的表达，增加体重、血清胰岛素和 NOx 水平，以及 miR-449a 的表达在链脲佐菌素诱导的糖尿病大鼠的睾丸损伤中。
我们的体内证据表明，硝酸盐治疗可能作为外源性 NO 供体对实验性糖尿病睾丸损伤具有有利影响，因为 NO 的生物利用度受损。
