黄地安消胶囊对糖尿病认知功能障碍大鼠神经保护作用及机制研究
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国家自然科学基金项目(81574040);国家中医药管理局临床基础研究项目(JDZX2015001);安徽省高校优秀青年人才支持计划重点项目(gxyq ZD2018053)


Neuroprotective Effect of Huangdi Anxiao Capsule in Rats with Diabetic Cognitive Dysfunction and Related Mechanisms
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    目的 通过观察黄地安消胶囊对糖尿病认知功能障碍(diabetic cognitive dysfunction,DCD)动物模型神经保护及Bax/Bcl-2凋亡信号通路的影响,探讨黄地安消胶囊治疗DCD、改善学习记忆功能的作用机制。方法 采用腹腔注射STZ联合Aβ25-35双侧海马注射复制DCD动物模型,期间予以高剂量(12 g/kg),中剂量(6 g/kg)及低剂量(3 g/kg)的黄地安消胶囊干预28 d,同时设立正常组、模型组以及二甲双胍和多奈哌齐组,每组10只。Morris水迷宫实验测试各组大鼠逃避潜伏期,大鼠尾静脉取血检测大鼠模型复制前及给药前后空腹血糖变化,苏木精-伊红染色观察各组大鼠海马神经细胞损伤情况,免疫荧光法观察各组大鼠海马Aβ清除情况,Western blot法检测大鼠海马神经细胞Bax、Bcl-2的蛋白表达量,qRT-PCR法检测Bax、Bcl-2的mRNA含量。结果 与正常组比较,模型组大鼠空腹血糖水平和逃避潜伏期明显升高(P<0.05),海马神经细胞损伤较重,Aβ沉积较多,Bax蛋白表达量及mRNA含量明显升高(P<0.05),Bcl-2蛋白表达量及mRNA含量明显降低(P<0.05);与模型组比较,黄地安消胶囊中剂量组具有最好的疗效,大鼠空腹血糖水平和逃避潜伏期明显降低,海马神经细胞损伤较轻,Aβ沉积较少,Bax蛋白表达量及mRNA含量明显降低(P<0.05),Bcl-2蛋白表达量及mRNA含量明显升高(P<0.05)。结论 黄地安消胶囊对DCD大鼠的学习记忆能力有明显改善作用,能够降低血糖,改善DCD大鼠海马神经细胞的损伤,清除Aβ沉积,其作用机制可能与调控Bax/Bcl-2凋亡信号通路有关。

    Abstract:

    Objective To investigate the neuroprotective effect of Huangdi Anxiao Capsule and its effect on Bax/Bcl-2 apoptotic signaling in a rat model of diabetic cognitive dysfunction (DCD), as well as the mechanism of action of Huangdi Anxiao Capsule in treating DCD and improving learning and memory functions. Methods A rat model of DCD was established by the intraperitoneal injection of streptozotocin combined with injection of Aβ25-35 into the bilateral hippocampus. High (12 g/kg)-, middle (6 g/kg)-, and low-dose (3 g/kg) Huangdi Anxiao Capsule was used for 28 days, and normal group, model group, metformin group, and donepezil group were also established, with 10 rats in each group. Morris water maze test was used to measure escape latency; blood samples were collected from the caudal vein to measure the change in fasting blood glucose before modeling and before and after administration; HE staining was used to observe the damage of hippocampal neurons; immunofluorescence assay was used to observe the clearance of hippocampal Aβ; Western blot was used to measure the protein expression of Bax and Bcl-2 in hippocampal neurons, and qRT-PCR was used to measure the mRNA expression of Bax and Bcl-2. Results Compared with the normal group, the model group had significant increases in fasting blood glucose and escape latency (P<0.05), significantly greater damage of hippocampal neurons and Aβ deposition, and significant increases in the protein and mRNA expression of Bax (P<0.05), as well as significant reductions in the protein and mRNA expression of Bcl-2 (P<0.05). Compared with the model group, the middle-dose Huangdi Anxiao Capsule group had the best clinical outcome, with significant reductions in fasting blood glucose, escape latency, damage of hippocampal neurons, Aβ deposition, and protein and mRNA expression of Bax (P<0.05) and significant increases in the protein and mRNA expression of Bcl-2 (P<0.05). Conclusion Huangdi Anxiao Capsule can significantly improve learning and memory abilities, reduce blood glucose, alleviate the damage of hippocampal neurons, and clear the deposition of Aβ in DCD rats, possibly by regulating the Bax/Bcl-2 apoptotic signaling pathway.

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宣玮婷,蔡 标,叶 婷,高华武,方朝晖,叶 树,王 艳,汪 瀚.黄地安消胶囊对糖尿病认知功能障碍大鼠神经保护作用及机制研究[J].安徽中医药大学学报,2020,39(2):63-68

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  • 在线发布日期: 2020-04-10