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目的:观察脑还丹对快速老化(SAMP/8)小鼠学习记忆能力及海马β-淀粉样蛋白前体蛋白(APP)、肽基脯氨酰顺反异构酶(Pin1)与高迁移率族蛋白Bl(HMGB1)mRNA表达的影响,探讨脑还丹防治阿尔茨海默病(AD)的作用机制。方法:选用6月龄雄性SAMP/8小鼠共30只,随机分为脑还丹高、低剂量组和模型组,另选用6月龄SAMP/1小鼠10只为正常对照组。高、低剂量组分别给予脑还丹84,21 g·kg-1ig;模型组、空白组给予双蒸水10 mL·kg-1,1次/d,连续8周。用Morris水迷宫方法测试小鼠的定位航行和空间探索能力,测试后每组取8只小鼠断头处死,无菌条件下剥出全脑,小心分离海马组织,采用实时荧光定量PCR(qRT-PCR)法检测海马组织中APP,Pin1,HMGB1 mRNA表达。结果:6月龄SAMP/8雄鼠的学习记忆能力明显低于同月龄SAMR/1雄鼠,表现为逃避潜伏期从第2天起显著延长,原平台象限停留时间缩短。脑还丹治疗8周后,SAMP/8小鼠逃避潜伏期明显缩短(P<0.05)。SAMR/1小鼠和用药各组小鼠的记忆保持能力比SAMP/8小鼠强,尤其以脑还丹高剂量组更明显(P<0.05)。与正常组比较,模型组APP mRNA相对表达量上调;与模型组比较,脑还丹高、低剂量组APP mRNA表达下调(P<0.05),高剂量组APP mRNA表达明显低于低剂量组(P<0.05)。与正常对照组比较,模型组Pin1 mRNA表达下调;与模型组比较,脑还丹高、低剂量组Pin1 mRNA表达上调(P<0.05),高剂量组Pin1 mRNA表达显著低于低剂量组(P<0.05);与正常组比较,模型组HMGB1 mRNA表达上调;与模型组比较,脑还丹高、低剂量组HMGB1 mRNA表达下调(P<0.05),高剂量组HMGB1 mRNA表达明显低于低剂量组(P<0.05)。结论:脑还丹治疗8周可改善SAMP/8小鼠的学习能力和记忆缺损。脑还丹可能通过下调SAMP/8小鼠APP,HMGB1 mRNA的表达,上调Pinl mRNA表达,从源头上阻断老年斑及神经元纤维缠结的形成,这可能是脑还丹防治AD的主要作用点之一。
AIM: To observe the effects of Naoxu Dan on learning and memory abilities and the changes of hippocampal β-amyloid precursor protein (APP), peptidyl prolyl trans-isomerase (Pin1) and high mobility (HMGB1) mRNA expression, explore the role of Naoban Dan in the prevention and treatment of Alzheimer’s disease (AD) mechanism. Methods: Thirty male SAMP / 8 male mice at 6 months old were randomly divided into three groups: model group (n = 10) and model control group (n = 10). The model group and the blank group were given distilled water 10 mL · kg-1, once a day for 8 weeks. Morris water maze method was used to test the positioning navigation and space exploration ability of mice. After the test, 8 mice in each group were decapitated and the whole brain was stripped under aseptic conditions. The hippocampus tissues were carefully separated and quantified by real-time fluorescence quantitative PCR (qRT -PCR) was used to detect the mRNA expression of APP, Pin1 and HMGB1 in hippocampus. Results: The learning and memory abilities of 6-month-old male SAMP / 8 male mice were significantly lower than those of the same age male SAMR / 1 male mice. The escape latency was significantly prolonged from the second day and the residence time of the original platform quadrant was shortened. After 8 weeks of treatment, the escape latency of SAMP / 8 mice was significantly shorter (P <0.05). The memory retention ability of SAMR / 1 mice and mice in each group was stronger than that of SAMP / 8 mice, especially in the high dosage of BND (P <0.05). Compared with the normal group, the expression of APP mRNA in the model group was up-regulated. Compared with the model group, the expression of APP mRNA was down-regulated in the high dose and high dose groups (P <0.05), while the expression of APP mRNA in high dose group was significantly lower than that in the low dose group P <0.05). Compared with the normal control group, Pin1 mRNA expression was down-regulated in model group. Pin1 mRNA expression was up-regulated in high and low dose groups (P <0.05), and Pin1 mRNA expression in high dose group was significantly lower than that in low dose group <0.05). Compared with the normal group, the expression of HMGB1 mRNA in the model group was up-regulated. Compared with the model group, the expression of HMGB1 mRNA in the high-dose and low-dose group was significantly decreased (P <0.05) Group (P <0.05). Conclusion: Naohuan Dan treatment for 8 weeks can improve learning ability and memory impairment in SAMP / 8 mice. Naohuan Dan may inhibit the formation of senile plaques and neurofibrillary tangles by down-regulating the expression of APP and HMGB1 mRNA and up-regulating Pinl mRNA expression in SAMP / 8 mice, which may be the main role of Noban in the prevention and treatment of AD one.