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Pharmacological Effects And Mechanism Of Six Happy Squares On Alzheimer 's Disease

Posted on:2017-05-02Degree:MasterType:Thesis
Country:ChinaCandidate:M H LiFull Text:PDF
GTID:2174330482484924Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
This paper is divided into three parts,1. In SH-SY5Y cell model of Aβ1-42 induced injury, observe the six class Kanxinsan influence on the survival rate, and compare the six class of Kaixinsan; 2. The six kinds of Kaixinsan on D-galactose and sodium nitrite due to the AD model improved the learning and memory ability of mice, and observe their effects on mice in hippocampus BDNF, Tau protein, p-Tau protein, Aβ, Ach, AchE and serum NT-proBNP, obtained better role of class, and the ratio is discussed based on the results of the study; 3. The 1st and 2nd in the fast aging mice, (SAM) AD model, pharmacological effect and mechanism of further research the better class party.Objective:This paper research the first six Kaixin powder the pharmacological action of these anti AD, screened has a good effect in order, a preliminary analysis of the different proportion of compatibility and pharmacological effects have different emphases, and preliminary exploration of its mechanism, to in-depth study of Kaixin powder the pharmacological effects of ad provided the basis for.Methods:In the first part of the study, by 20 mol · L-1 Aβ 1-42 effect on SH-SY5Y cells cultured for 24 hours to establish a cell model of Alzheimer’s disease, given the Kaixin powder class high, medium and low dose (3.570g mg · kg-1,1.785g · kg-1 and 0.892g · kg-1). MTT assay was used to detect the different doses of six Kaixin powder decoction on the survival rate of Aβ1-42 induced SY5Y cells of influence.The second part of Kunming mice, intraperitoneal injection of D-galactose and sodium nitrite for 8 weeks, after the establishment of a mouse model of Alzheimer’s, giving the six Kaixin powder decoction (3.570g mg · kg-1,1.785g · kg-1 and 0.892g · kg-1) and the positive drug (huperzine A 0.05 mg · kg-1), continuous intragastric administration after 35 days. The Morris water maze test to evaluate each animal learning and memory ability, the content of BDNF in the hippocampus of mice with Western blotting detected, ELISA method for the detection of each group of mice hippocampal Tau protein, p-Tau protein, Aβ, Ach, AchE and NT-proBNP content.The third part of the study based on the previous 1 and 2, we believe that the Kaixinsan of Qianjin yaofang and Kxinwan of Yimenfang in cellular and animal models of Alzheimer’s disease have shown better than other kind of role, this part in the fast aging model mice, to observe the two classes of fast aging model improved the learning and memory ability of mice, and the influence on the rapid aging of hippocampus and cortex in a mouse model of BDNF, Tau protein, p-Tau protein, Aβ, Ach, AchE and serum NT-proBNP, and the 1st and 2nd parts to verify the obtained results, and increased in the cortex of various indicators of animal. Rapid aging model mice given two Kaixin powder decoction and positive drug (3.570g mg · kg-1,1.785g · kg-1,0.892g · kg-1 and huperzine 0.05 mg · kg-1), continuous intragastric administration after 35 days, the capability of learning and memory in Morris water maze test to evaluate the animals in each group, the content of BDNF in the Western blotting method detected in hippocampus and cortex,, ELISA method was detected in hippocampus and cortex, Tau protein, p-Tau protein, Aβ, Ach, AchE and serum NT-proBNP in content.Results:The results of the first part, compared with the model group, Kaixinsan of Qianjin yaofang, in dose of cell survival rate was significantly higher, with significant difference (P< 0.01); the Kaixinsan of Qianjin yaofang high and low dose group, Kaixinwan of Yimenfang high, medium and low dose, Kaixinsan of Yimenfang medium dose, Dingfzhiwan of Gujin luyan high dose and middle dose, Dingzhi xiaowan of Beiji qianjinyaofang medium doses of cell survival rate increased, with statistical significance (P< 0.05). According to different point of view, Kaixinsan of Qianjin yaofang, scattered high and low dose group and Kaixinwan of Yimenfang high, medium and low dose group and model group were compared to improve the survival rate of the cell model of Alzheimer’s disease, and other classes of cell survival rate improvement is not obvious.The result of the second part, Kaixinsan of Qinjin yaofang high and middle dose could significantly improve the AD model of learning and memory ability of mice, significantly increased BDNF and Ach in the hippocampus, significantly reduce the AchE, A (3 and Tau in the hippocampus of the beta protein, p-Tau protein and serum NT-proBNP content, pharmacological effects the most comprehensive analysis, and according to the weight of its role in the Tau protein is prominent; Most significant dose of Kaixinwan of Yimenfang optimization of the evaluation of the ability of learning and memory, were significantly increased in hippocampus of AD model mice in BDNF, Ach content decreased significantly in hippocampus of AD model mice in Aβ and Tau protein, p-Tau protein content and AchE activity, decreased the content of NT-proBNP in serum of AD mice, pharmacological function, and according to the weight analysis for its role in the Tau protein is also prominent; A few doses of Kaixinsa of Yimenfang, Dingzhi xiaowan of Beiji Qianjinyaofang and Dingzhiwan of Gujin Luyan significantly optimize the evaluation of the learning and memory ability of the index was significantly higher in AD model mice, Ach content, significantly reduced the AD model mice in the hippocampus of Aβ and Tau protein, p-Tau protein content and the activity of AchE, significantly reduced the AD model mice and serum NT-proBNP levels, pharmacological effect is not very significant; The high, middle and low dose of Buxintang of Qianjinyi were not seen in the Alzheimer’s disease animal model. The results suggest that Kaixinsan of Qinjin yaofang on a mouse model of Alzheimer’s disease is the most comprehensive, the medical side Kaixinwan of Yimenfang and effect of the two parties in the tau protein is more prominent. According to the preliminary analysis of the compatibility proportion, pharmacological effects of most comprehensive Kaixinsan of Qianjin yaofang reuse Poria and Acorus gramineus Soland two flavor powder, reminds us, Poria and Acorus gramineus Soland may play in the treatment of AD is one of the main factors.The result of the third part, in the hippocampus, Kaixinsan of Qianjin yaofang and Kaixinwan of Yimenfang can effectively increased the contents of BDNF in hippocampus in the animal model, increase the content of Ach, reduce the activity of AchE, reduce the Aβ content, decreased Tau protein and p-Tau protein content, with the more obvious; at the same time, the Kaixinsan of Qinjin yaofang can effectively increase the content of Ach in the cortex, reduce the activity of AchE, reduce the content of Aβ protein and p-Tau protein, decreased Tau content; the Kxinwan of Yimenfang group can effectively increase the content of Ach, reduce the activity of AchE, lower Tau protein and p-Tau protein content however, the indexes of hippocampal cortex in rats than in worse. Results suggest that Kaixinsan of Qinjin yaofang and Kxinwan of Yimenfang in senescence accelerated mouse model, has been with 1 st and 2nd. In addition, in senescence accelerated mouse model, effect of these two kinds of hippocampus than the skin layer effects to some more.Conclusion:By screening the six Kaixin powder category that Kaixinsan of Qianjin yaofang and Kxinwan of Yimenfang on Alzheimer’s disease model has a good therapeutic effect may be related to inhibiting the and increased the content of Ach and decrease the activity of AchE is more closely related the hyperphosphorylation of Tau protein, in terms of compatibility proportion, Poria and Acorus gramineus Soland may play its treatment of AD is one of the factors. Suggest that the two class has good anti Alzheimer’s potential.
Keywords/Search Tags:Kaixin san formμlas, Alzheimer, AD model, Tau protein, Cholinesterase
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