Pharmacy Department, People's Hospital of Henan Province, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China.
J Tradit Chin Med. 2018 Dec;38(6):890-895.
To examine the effects of Cuzhi liquid on learning and memory abilities in a mouse model of Alzheimer's disease (AD).
One hundred mice were divided into the normal, AD model, piracetam group, Cuzhi liquid low dose and Cuzhi liquid high dose, each group 20 mice. The AD mouse model was induced by daily intraperitoneal injection of D-galactose and sodium nitrite. AD mice then received intragastric administration of piracetam or Cuzhi liquid for 60 d, and changes in learning and memory abilities were assessed using the water maze test. The activity of acetylcholinsterase (AchE) and monamine oxidase (MAO), and the levels of nitrogen monoxidum (NO) and malonaldehyde (MDA), were measured in brain tissues. Amyloid protein deposition was assessed by methyl violet staining, and B-cell lymphoma-2 (Bcl-2) expression in the hippocampal cornus ammonis 1 region was detected by immunohistochemistry.
In the water maze test, the escape latency of the model group was longer than that of the normal group (P < 0.01). The escape latency of the three using drug treatment groups was significantly less than that of the normal group (P < 0.05). The activity of AchE and MAO, and the levels of NO and MDA, in the brain of the model group were significantly higher than that of the normal group (P < 0.01), but significantly reduced in the three drug treatment groups compared with the model group (P < 0.05). AchE activity showed a greater reduction in the two Cuzhi liquid groups compared with the piracetam group (P < 0.01), to levels similar to the normal group. There were no differences in MAO activity or NO levels between the three drug treatment groups, while MDA levels were reduced more in the high-dose Cuzhi liquid group compared with the other treatment groups (P < 0.01). Hippocampal Bcl-2 expression was significantly reduced in the model group compared with the normal group (P < 0.01), but significantly improved in the three drug treatment groups (P < 0.05). The high-dose Cuzhi liquid group showed a significantly greater recovery in Bcl-2 expression compared with the other treatment groups.
Cuzhi liquid can improve learning and memory impairment in an AD mouse model. The mechanism of action may relate to reduced AchE and MAO activity, and reduced NO and MDA levels, in the brain, and improved Bcl-2 expression, an inhibitor of apoptosis.
观察刺蒺藜液对阿尔茨海默病(AD)模型小鼠学习记忆能力的影响。
将 100 只小鼠随机分为正常组、AD 模型组、吡拉西坦组、刺蒺藜液低剂量组和刺蒺藜液高剂量组,每组 20 只。采用腹腔注射 D-半乳糖和亚硝酸钠的方法诱导 AD 模型小鼠,造模成功后,吡拉西坦组和刺蒺藜液低、高剂量组分别给予吡拉西坦和刺蒺藜液灌胃 60 d,采用水迷宫实验检测各组小鼠学习记忆能力的变化,采用比色法检测各组小鼠脑组织中乙酰胆碱酯酶(AchE)和单胺氧化酶(MAO)活性,采用硝酸还原酶法检测各组小鼠脑组织中一氧化氮(NO)和丙二醛(MDA)水平,采用甲基紫染色法检测各组小鼠脑组织中淀粉样蛋白沉积情况,采用免疫组织化学法检测各组小鼠海马 CA1 区 B 细胞淋巴瘤-2(Bcl-2)的表达。
水迷宫实验结果显示,与正常组比较,模型组小鼠逃避潜伏期延长(P<0.01);与模型组比较,各用药组小鼠逃避潜伏期均缩短(P<0.05)。与正常组比较,模型组小鼠脑组织中 AchE 和 MAO 活性、NO 和 MDA 水平均升高(P<0.01),各用药组小鼠脑组织中 AchE 和 MAO 活性、NO 和 MDA 水平均降低(P<0.05),且刺蒺藜液低、高剂量组 AchE 活性降低更明显(P<0.01),与正常组比较差异无统计学意义。各用药组间 MAO 活性和 NO 水平比较,差异均无统计学意义,刺蒺藜液高剂量组 MDA 水平降低更明显(P<0.01)。与正常组比较,模型组小鼠海马 CA1 区 Bcl-2 表达降低(P<0.01),各用药组小鼠海马 CA1 区 Bcl-2 表达升高(P<0.05),且刺蒺藜液高剂量组 Bcl-2 表达升高更明显(P<0.01)。
刺蒺藜液可改善 AD 模型小鼠学习记忆障碍,其作用机制可能与降低脑组织中 AchE 和 MAO 活性、减少 NO 和 MDA 生成、提高 Bcl-2 表达有关。