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链脲佐菌素(STZ)诱导的糖尿病以剂量依赖方式影响大鼠组织中的微量元素含量。

Streptozotocin (STZ)-Induced Diabetes Affects Tissue Trace Element Content in Rats in a Dose-Dependent Manner.

作者信息

Karganov Mikhail Yu, Alchinova Irina B, Tinkov Alexey A, Medvedeva Yulia S, Lebedeva Marina A, Ajsuvakova Olga P, Polyakova Margarita V, Skalnaya Margarita G, Burtseva Tatiana I, Notova Svetlana V, Khlebnikova Nadezhda N, Skalny Anatoly V

机构信息

Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.

Yaroslavl State University, 150003, Yaroslavl, Russia.

出版信息

Biol Trace Elem Res. 2020 Dec;198(2):567-574. doi: 10.1007/s12011-020-02090-2. Epub 2020 Mar 6.

Abstract

The objective of the present study was investigation of tissue trace element distribution in a streptozotocin model of DM1 in rats. DM1 was modeled in 2-month-old male Wistar rats (n = 30) using intraperitoneal injection of 45 mg/kg b.w. (STZ1) and 55 mg/kg b.w. streptozotocin (STZ2), whereas control animals were injected with physiological saline. The rats were subjected to oral glucose tolerance test (OGTT) and HbA1c level assessment at day 14. At day 30, blood serum, liver, kidney, and heart samples were collected for tissue trace element assessment using inductively coupled plasma mass spectrometry (ICP-MS). STZ-treated rats were characterized by lack of significant weight gain and elevated HbA1c and blood glucose levels. ICP-MS analysis demonstrated a dose-dependent accumulation of Cu, Mn, Mo, and Se levels in the liver. Correspondingly, the dose-dependent increase in renal Cu, Mn, V, and Zn levels was significant, whereas the observed trend for kidney V and Mo accumulation was nearly significant. The patterns of trace element content in the myocardium of STZ-exposed rats were quite different from those observed for liver and kidney. Only cardiac Zn content was characterized by a significant decrease. Serum Co, Cr, Cu, Se, V, and Mo levels were characterized by a significant decrease in response to STZ-induced diabetes. Generally, the obtained data demonstrate that diabetes is associated with altered copper, manganese, molybdenum, chromium, and vanadium handling. In turn, only altered Zn status may provide a link to diabetic cardiotoxicity. However, the particular mechanisms of both impaired metal handling in STZ diabetes and their potential anti-diabetic activity require further investigation.

摘要

本研究的目的是调查链脲佐菌素诱导的大鼠1型糖尿病模型中组织微量元素的分布情况。采用腹腔注射45mg/kg体重的链脲佐菌素(STZ1)和55mg/kg体重的链脲佐菌素(STZ2),在2月龄雄性Wistar大鼠(n = 30)中建立1型糖尿病模型,而对照动物注射生理盐水。在第14天对大鼠进行口服葡萄糖耐量试验(OGTT)和糖化血红蛋白(HbA1c)水平评估。在第30天,采集血清、肝脏、肾脏和心脏样本,使用电感耦合等离子体质谱法(ICP-MS)进行组织微量元素评估。经链脲佐菌素处理的大鼠表现为体重无显著增加,糖化血红蛋白和血糖水平升高。ICP-MS分析表明,肝脏中铜、锰、钼和硒水平呈剂量依赖性积累。相应地,肾脏中铜、锰、钒和锌水平的剂量依赖性增加显著,而观察到的肾脏中钒和钼积累趋势接近显著。链脲佐菌素处理大鼠心肌中的微量元素含量模式与肝脏和肾脏中观察到的模式有很大不同。只有心脏锌含量显著降低。血清钴、铬、铜、硒、钒和钼水平因链脲佐菌素诱导的糖尿病而显著降低。总体而言,获得的数据表明糖尿病与铜、锰、钼、铬和钒的代谢改变有关。反过来,只有锌状态的改变可能与糖尿病心脏毒性有关。然而,链脲佐菌素诱导的糖尿病中金属代谢受损及其潜在的抗糖尿病活性的具体机制需要进一步研究。

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