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目的探讨吡格列酮对β淀粉样蛋白(Aβ)25-35所致的阿尔茨海默病(AD)大鼠学习记忆障碍的改善作用及脑源性神经营养因子(BDNF)及酪氨酸激酶受体B(Trk B)海马区表达的作用。方法随机将40只SD大鼠分为痴呆模型组、对照组、吡格列酮高剂量组,吡格列酮低剂量组(每组10只),对照组双侧海马区注射生理盐水,其余3组以双侧海马CA1区注射Aβ25-35制备痴呆大鼠模型,造模后,高、低吡格列酮组分别用80 mg/kg及40 mg/kg,其余各组予生理盐水灌胃。Morris水迷宫检测痴呆大鼠学习记忆能力,免疫组化法检测双侧海马BDNF、Trk B阳性细胞的数目,Western blot的方法观察BDNF、Trk B表达量的变化。结果 Morris水迷宫检测显示:与模型组比较,吡格列酮治疗组潜伏期明显缩短(P<0.05),穿越平台次数明显增多(P<0.05),平台滞留时间明显延长(P<0.05)。免疫组化法检测显示模型组大鼠海马区BDNF及Trk B阳性细胞数较对照组明显减少,吡格列酮组较模型组明显增加(P均<0.05),低剂量组、高剂量组无明显差异。Western blot方法显示模型组大鼠海马区BDNF及Trk B表达量较对照组明显减少,吡格列酮组较模型组明显增加(P均<0.05),高、低剂量吡格列酮组无明显差异。结论海马CA1区注射Aβ25-35可致大鼠学习记忆障碍,吡格列酮可改善AD大鼠的学习记忆功能,其机制可能与调节脑内BDNF及特异性高亲和Trk B通路有关,从而为阿尔茨海默病的治疗提供新的理论依据。
Objective To investigate the effects of pioglitazone on the learning and memory impairments of Alzheimer’s disease (AD) rats induced by β-amyloid (Aβ) 25-35 and the effects of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (Trk B) hippocampus expression. Methods 40 SD rats were randomly divided into dementia model group, control group, pioglitazone high-dose group and pioglitazone low-dose group (10 rats in each group). The control group was injected with normal saline on hippocampus. The other three groups were treated with bilateral hippocampus CA1 area injection of Aβ25-35 rat model of dementia, modeling, high and low pioglitazone group were 80 mg / kg and 40 mg / kg, the remaining groups were given normal saline. The Morris water maze was used to detect the learning and memory ability of dementia rats. The number of BDNF and Trk B positive cells in bilateral hippocampus was detected by immunohistochemistry. The expression of BDNF and Trk B was observed by Western blot. Results Morris water maze test showed that compared with the model group, pioglitazone significantly reduced the latency (P <0.05), the number of crossing platform significantly increased (P <0.05), and the platform retention time was significantly longer (P <0.05). Immunohistochemistry showed that the number of BDNF and Trk B positive cells in hippocampus in model group was significantly decreased compared with that in control group. The pioglitazone group was significantly higher than that in model group (all P <0.05). There was no significant difference between low dose group and high dose group. Western blot showed that the expression of BDNF and Trk B in hippocampus in model group was significantly decreased compared with that in control group. The pioglitazone group was significantly increased compared with model group (all P <0.05), and no significant difference was found between high and low dose pioglitazone groups. Conclusion Aβ25-35 can induce learning and memory impairment in hippocampal CA1 area of rats, and pioglitazone can improve the learning and memory function of AD rats. The mechanism may be related to the regulation of brain BDNF and specific high-affinity Trk B pathway, The treatment of Hyperthermia provides a new theoretical basis.