Tanshinone IIA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis
Tanshinone IIA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis
复制标题
丹参酮 IIA 通过减弱内质网应激诱导的细胞凋亡对糖尿病大鼠海马依赖性认知障碍发挥神经保护作用
DOI：
10.1016/j.biopha.2018.05.040
复制
发表时间：
2018-08-01
影响因子：
7.5
通讯作者：
Xu, Linhao
中科院分区：
文献类型：
--
作者：
Chen, Jian;Bi, Yanli;Xu, Linhao
本研究旨在探讨丹参酮Ⅱ A（Tan Ⅱ A）抑制糖尿病大鼠海马神经元凋亡的机制。将SD大鼠随机分为对照组、糖尿病组和不同剂量（2或4 mg/kg/d）的Tan IIA治疗组。用链脲佐菌素（STZ）诱发大鼠糖尿病。STZ治疗后2天，Tan IIA组大鼠腹腔注射Tan IIA，而对照组和糖尿病组大鼠注射等体积的生理盐水。6周后，进行一次性物体识别任务和Morris水迷宫测试。糖尿病组学习记忆能力较对照组明显下降（P < 0.05）。谭IIA拯救了依赖于校园的记忆。超氧化物歧化酶（SOD）活性降低，活性氧（ROS）产生、丙二醛（MDA）含量和78-kDa葡萄糖调节蛋白（Grp 78）、生长停滞和DNA损伤诱导基因153与对照组相比，糖尿病大鼠海马中CHOP/GAD 153和切割的caspase-3水平增加，糖尿病组神经细胞凋亡率明显高于对照组（P < 0.01）。但丹参Ⅱ A通过诱导SOD活性降低MDA含量及GRP 78和CHOP表达。Tan IIA通过抑制内质网（ER）应激激活，减轻神经元凋亡，改善学习和记忆。
This study aimed to investigate the mechanism by which tanshinone IIA (Tan IIA) suppresses neuronal apoptosis in the hippocampus of diabetic rats. Sprague-Dawley (SD) rats were randomly divided into the following four groups: a control group, a diabetes group and diabetes groups treated with different doses (2 or 4 mg/kg/day) of Tan IIA. Streptozotocin (STZ) was injected into the rats to induce diabetes. Two days after STZ treatment, Tan IIA was intraperitoneally administered to rats in the Tan IIA groups, whereas an equal volume of saline was administered to rats in the control and diabetes groups. After 6 weeks, a one-trial object recognition task and the Morris water maze were applied. The diabetes group displayed notably decreased learning and memory abilities compared with the control group (P < 0.05). Tan IIA rescued hippocampus-dependent memory. Superoxide dismutase (SOD) activity was reduced, and reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and 78-kDa glucose-regulated protein (Grp78), growth arrest and DNA damage-inducible gene 153 (CHOP/GAD153) and cleaved caspase-3 levels were increased in the hippocampus of diabetic rats compared with that of control rats, changes that were accompanied by an increase in neuronal apoptosis in diabetic rats compared with control rats (P < 0.01). However, Tan IIA reduced the MDA content and GRP78 and CHOP expression by inducing SOD activity. Tan IIA attenuated neuronal apoptosis and improved learning and memory by suppressing endoplasmic reticulum (ER) stress activation.