Department of Pathology, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Road, Chaoyang District, Beijing 100029, China.
J Ethnopharmacol. 2011 Sep 2;137(2):1035-46. doi: 10.1016/j.jep.2011.07.031. Epub 2011 Jul 20.
Tong Luo Jiu Nao (TLJN) is a modern Chinese formula based on Traditional Chinese Medicine theory that has been used to treat ischemic cerebral stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanism of the TLJN effect on Alzheimer's disease (AD).
To investigate the effect of TLJN on β-amyloid-degrading enzymes and learning and memory in the AD rat brain.
AD rats whose disease was induced by Aβ(25-35) injection into the bilateral hippocampus CA1 region were subjected to intragastric administration of various preparations. The experimental animals were healthy male Sprague-Dawley rats which were randomly divided into normal, sham, model, TLJN min, TLJN max and donepezil hydrochloride groups. Spontaneous alternation and passive avoidance behavior, which are regarded as measures of spatial learning and memory, were investigated using Y-maze testing. Western blotting and immunohistochemistry were used to observe the therapeutic effect of TLJN on the deposits of amyloid plaque and on the expression of synaptophysin, insulin-degrading enzyme and neprilysin.
Y-maze results showed that the AD model group presented with spatial learning and memory impairments. Hematoxylin-eosin and Congo red staining indicated neuronal impairment and deposits of amyloid plaque in the model group and these results were consistent with their learning and memory deficits in the Y-maze. The TLJN-treated groups exhibited prolonged a cavity delitescence, decreased arm entries and improvement in learning and memory. Moreover, the structure of the neurons of the treated groups was restored and the expression of synaptophysin increased in both the hippocampus and cortex. In addition, their levels of insulin-degrading enzyme and neprilysin in the cortex and hippocampus were upregulated and the amyloid plaque was decreased.
TLJN can improve learning and memory, up-regulate insulin-degrading enzyme and neprilysin levels, promote the degrading of Aβ and clear amyloid plaque from the AD rat brain. In future, TLJN may have significant therapeutic potential in the treatment of AD patients.
通络救脑（TLJN）是一种基于中医理论的现代中药配方，用于治疗缺血性脑卒中和血管性痴呆。TLJN 属于民族药理学药物家族。在这项研究中，我们研究了 TLJN 对阿尔茨海默病（AD）的作用机制。
研究 TLJN 对 AD 大鼠脑内β-淀粉样蛋白降解酶和学习记忆的影响。
将 Aβ（25-35）注入双侧海马 CA1 区诱导 AD 大鼠，给予不同制剂灌胃。实验动物为健康雄性 Sprague-Dawley 大鼠，随机分为正常、假手术、模型、TLJN 小、TLJN 大、盐酸多奈哌齐组。采用 Y 迷宫测试观察自发交替和被动回避行为，作为空间学习和记忆的测量指标。采用 Western blot 和免疫组织化学观察 TLJN 对淀粉样斑块沉积和突触素、胰岛素降解酶、neprilysin 表达的治疗作用。
Y 迷宫结果显示 AD 模型组出现空间学习记忆障碍。苏木精-伊红和刚果红染色显示模型组神经元损伤和淀粉样斑块沉积，与 Y 迷宫中的学习记忆缺陷一致。TLJN 治疗组潜伏期延长，臂进入次数减少，学习记忆能力提高。此外，治疗组神经元结构得到恢复，海马和皮质突触素表达增加。同时，皮质和海马胰岛素降解酶和 neprilysin 水平上调，淀粉样斑块减少。
TLJN 可改善学习记忆，上调胰岛素降解酶和 neprilysin 水平，促进 Aβ 降解，清除 AD 大鼠脑内淀粉样斑块。未来，TLJN 可能在 AD 患者的治疗中具有重要的治疗潜力。
