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牛磺酸可改善 STZ 诱导的糖尿病 Wistar 大鼠氧化应激诱导的炎症和内质网应激介导的睾丸损伤。

Taurine ameliorates oxidative stress induced inflammation and ER stress mediated testicular damage in STZ-induced diabetic Wistar rats.

机构信息

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054, India.

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054, India.

出版信息

Food Chem Toxicol. 2019 Feb;124:64-80. doi: 10.1016/j.fct.2018.11.055. Epub 2018 Nov 26.

Abstract

One of the major consequences of diabetes is reproductive dysfunction but the fundamental mechanisms are still poorly known. The objective of the present study was to explore the beneficial role of taurine against streptozotocin induced testicular dysfunctions in diabetic male Wister rats and understanding the underlying intricate molecular mechanisms. Exposure to streptozotocin (50 mg kg body weight, i.p., once) elevated blood glucose level, induced testicular histological alterations and reduced testis-to-body weight ratio, serum testosterone, testicular markers and activity of antioxidant enzymes. Generation of ER stress (increased expression of calpain-1, caspase-12 and upregulation of CHOP, GRP78 via eIF2α signaling), translocation of NF κB in the nucleus (leading to the upregulation in the levels of inflammatory cytokines), activation of mitochondria dependent apoptotic pathway and DNA fragmentation were revealed from this study. However, administration of taurine at a dose of 100 mg kg body weight for 6 weeks post diabetic induction, successfully ameliorated all these adverse effects. Thus, taurine, as a potential therapeutic agent, may hold promise in preventing oxidative and ER stress mediated diabetic testicular complications in rats.

摘要

糖尿病的主要后果之一是生殖功能障碍,但基本机制仍知之甚少。本研究的目的是探讨牛磺酸对链脲佐菌素诱导的糖尿病雄性 Wister 大鼠睾丸功能障碍的有益作用,并了解潜在的复杂分子机制。链脲佐菌素(50mg/kg 体重,腹腔注射,一次)暴露可升高血糖水平,诱导睾丸组织学改变,并降低睾丸/体重比、血清睾酮、睾丸标志物和抗氧化酶活性。本研究揭示了内质网应激的产生(钙蛋白酶-1、半胱天冬酶-12 和 CHOP、GRP78 的表达增加通过 eIF2α 信号转导)、NF-κB 在核内易位(导致炎症细胞因子水平上调)、线粒体依赖性凋亡途径的激活和 DNA 片段化。然而,在诱导糖尿病后 6 周给予牛磺酸 100mg/kg 体重的剂量,可成功改善所有这些不良反应。因此,牛磺酸作为一种潜在的治疗剂,可能有望预防大鼠氧化应激和内质网应激介导的糖尿病睾丸并发症。

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