摘要
目的探究血竭素高氯酸盐(Dracorhodin perchlorate,DP)对阿尔茨海默病大鼠学习记忆及海马TGF-β1通路相关蛋白的影响。方法随机选取10只大鼠作为假手术组,其余大鼠建立AD模型,造模成功后分为模型组、多奈哌齐组(0.33 mg/kg)、DP低剂量组(10 mg/kg)、DP中剂量组(20 mg/kg)、DP高剂量组(30 mg/kg),所有大鼠均行灌胃治疗,假手术组及模型组给予等量生理盐水,治疗4周后,采用MWM实验检测大鼠学习记忆能力,免疫组化检测海马组织中Aβ的表达水平,实时荧光定量PCR(qRT-PCR)和蛋白免疫印迹(WB)检测海马组织中TGF-β1和SMAD2表达情况。结果与模型组相比,DP组大鼠逃避潜伏时间明显缩短,穿越平台的次数明显增加,大鼠海马组织中Aβ的表达水平显著降低(P<0.05),且呈剂量依赖性。Western blot检测结果显示,与模型组相比,DP组大鼠海马组织中TGF-β1表达水平显著升高(P<0.05),p-SMAD2的表达水平显著降低(P<0.05),且呈剂量依赖性。结论 DP能够改善AD模型大鼠的学习记忆,推测这一作用是通过调控海马组织中TGF-β1和p-SMAD2的表达水平实现的,为AD的临床治疗提供一定理论基础。
Objective To investigate the effect of dracorhodin perchlorate（ DP） on learning and memory and hippocampal TGF-β1 pathway-related proteins in Alzheimer disease rats. Methods Ten rats were randomly selected as sham operation group, and the other rats were established AD models; after the successful modeling they were divided into model group,donepezil group（ 0. 33 mg/kg）,DP low-dose group（ 10 mg/kg）,DP middle-dose group（ 20 mg/kg）, and DP high-dose group（ 30 mg/kg）. All rats were given intragastric administration,and sham operation group and model group were given the same amount of normal saline. After 4 weeks of treatment, the learning and memory abilities of rats were detected by MWM test, the expression levels of Aβ in hippocampus were detected by immunohistochemistry,and the real time fluorescent quantitative PCR（ qRT-PCR） and Western blot（ WB） were used to detect the expression of TGF-β1 and SMAD2 in the hippocampus. Results Compared with the model group, the escape latency time of DP group was significantly shortened, the number of traversing platforms of DP group was increased significantly,and the expression level of Aβ in hippocampus of rats in DP group was significantly decreased（ P〈0. 05）, and all those were dose-dependent. Western blot results showed that,compared with the model group, in the hippocampus of rats in the DP group, the TGF-β1 expression level was significantly increased（ P〈0. 05）, and the expression level of p-SMAD2 was decreased significantly（ P〈 0. 05）, in a dose-dependent manner. Conclusion DP can improve the learning and memory ability of AD model rats. It is speculated that this effect is achieved by regulating the expression levels of TGF-β1 and p-SMAD2 in hippocampal tissue,which provides a theoretical basis for the clinical treatment of AD.
作者
张路赢
马丹霞
杨艾堂
彭会明
ZHANG Lu-ying;MA Dan-xia;YANG Ai-tang;PENG Hui-ming(Department of Anatomy,Hubei College of Chinese Medicine,Jingzhou 434020,China;Department of Anatomy,School of Basic Medical Sciences,Huazhong University of Science and Technology,Wuhan 430030,China)
出处
《实用药物与临床》
CAS
2018年第6期627-631,共5页
Practical Pharmacy and Clinical Remedies
基金
湖北省自然科学基金资助项目(2015CFB079)
