Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Pharmacol Rep. 2019 Aug;71(4):713-720. doi: 10.1016/j.pharep.2019.03.012. Epub 2019 Mar 22.
Minocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats.
High fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment.
We induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment.
Minocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.
米诺环素是一种四环素类抗生素，具有抗炎和神经保护作用。在这里，我们确定米诺环素治疗 2 型糖尿病相关认知功能下降的大鼠的潜在疗效。
高果糖饮食（HFD）和低剂量链脲佐菌素（STZ；25mg/kg）用于诱导 Sprague-Dawley 大鼠糖尿病。测量这些动物的空腹血糖和血红蛋白（Hb）A1c。使用被动回避和高架十字迷宫试验测量认知参数。测量海马乙酰胆碱酯酶（AchE）、还原型谷胱甘肽（GSH）、细胞因子、趋化因子水平，并进行组织病理学评估。然后给糖尿病动物给予米诺环素（50mg/kg；15 天），并重新评估上述参数。在存在葡萄糖的情况下，进行 MTT 和乳酸脱氢酶（LDH）测定，以及有无米诺环素治疗的神经元细胞。
我们使用 HFD 和 STZ 在这些动物中诱导糖尿病。与对照组动物相比，动物的空腹血糖水平（>245mg/dl）和 HbA1c 较高。糖尿病显著降低了踏步潜伏期并增加了转移潜伏期。与对照组相比，糖尿病动物的 AchE、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和单核细胞趋化蛋白（MCP）-1显著升高，GSH 水平降低，CA1 和 CA3 神经元密度降低。米诺环素治疗部分逆转了上述神经行为和生化变化，并改善了糖尿病动物的海马神经元密度。细胞系研究表明葡萄糖介导的神经元死亡，而米诺环素治疗则大大逆转了这种死亡。
米诺环素主要通过其抗炎和抗氧化作用防止海马神经元丢失，从而部分逆转大鼠与糖尿病相关的认知功能下降。
