| [Background]Alzheimer’s disease (AD) is the prevalent neurodegenerative disease characterized clinically by progressive decline of intellectual abilities, including memory and reasoning. A large number of people are beginning to aware of this disease with the aged tendency of population and medicine development. Epidemiological study shows that morbidity and prevalence rate in each country is distinct which is relevant to the developing levels of nation, living standards and civilizations. The abroad data demonstrate that there are almost 36.5 million patients with dementia and an increase of 7.7 million patients each year, which the AD patients accounts for 50% to 70%. China is a populous country, in which more than 13% of the population over 60 years old, and the prevalence of AD is 3% to 5%. Thus, AD has become a vital public health problem in China.International scholars pose a large amount of exploration to AD, but its etiology and pathogenesis is still not clear. There are a good many hypotheses about AD pathological mechanism, such as inflammatory reaction, P-amyloid protein (Aβ) cascade theory hypothesis, oxidative stress, and Tau hyperphosphorylation, etc. However, there is no a hypothesis to well elaborate the progression of AD, and the treatment currently focused on alleviating the symptoms. Although a large number of clinical studies have confirmed the effectiveness of the drug and safety, its long-term treatment effect is not ideal and expensive, which results in poor patient compliance. Traditional Chinese Medicine take holism and syndrome differentiation as the core, that has certain advantages with a few effects, cheap and good compliance in treatment of dementia. Many physicians have their own experience and obtained a good curative effect. While the current clinical application is lack of standardization, pathogenesis of AD is not clear, so it is feasible to utilize the Traditional Chinese Medicine combined with modern medicine theory to treat the disease, which provides theoretical basis for Chinese medicine to remedy AD.[Objecting and methods]In order to further reveal the related mechanism of Chinese traditional medicine in treatment on AD, we performed the drug intervention to the AD rat model, using western blot to observe the expression levels of protein related to inflammatory reaction, and explore the Tianqi Yizhi granules based on "supplementing qi and activating blood circulation" method on protective effects against inflammatory reaction in AD rats.[Experimental study]Methods:AD animal model was established with Aβ1-42 injection in lateral ventricle of rats, and AD nerve inflammatory reaction was used to observe the proteins expression in brain tissue. The high, medium and low dosage of Tianqi Yizhi granules were given each day to treat the AD rats, and the huperzine treatment as positive control. Meanwhile, the blank and model group were given the equal amount of saline respectively for 30 days. The rats were sacrificed and the proteins in brain tissue were extracted, the western blot was applied for determination of protein expression in brain tissue of each group, and the possible mechanism of Tradition Chinese Medicine in treatment of AD rats was also discussed.Results:1. Compared with blank group, the expression levels of GFAP and Iba-1 in model group had significantly increased (p<0.01); 2. The expression of GFAP in high, medium and low dosage of Tianqi Yizhi granules group and huperzine group had respectively decreased by 65.12%,58.39%,35.15%, and 62.18%(p<0.05 or p<0.01). The expression of Ibal in high, medium and low dosage of Tianqi Yizhi granules group and huperzine group had respectively decreased by 71.63%,54.44%,50.58% and 13.02%(p<0.05); 3. Tianqi Yizhi granules and huperzine could significantly decreased the expression of phospho-p38/t-p38 (p<0.05). The expression of phospho-p38/t-p38 in high, medium and low dosage of Tianqi Yizhi granules group and huperzine group had respectively decreased by 56.17%,38.83%, 30.51% and 59.66%(p<0.05). The expression of phospho-p38/t-p38 in high, medium and low dosage of Tianqi Yizhi granules group had decreased by 58.88%,41.29% and 17.13%. However, huperzine had no significant influence of NF-kappa B activation; 4. Tianqi Yizhi granules could significantly decreased the expression of iNOS and COX2 in brain tissue of rats (p<0.01). The expression of iNOS in high, medium and low dosage of Tianqi Yizhi granules group had decreased by 92.30%,72.85% and 40.95%. The expression of COX in high, medium and low dosage of Tianqi Yizhi granules group had decreased by 84.19%, 75.30% and 48.64%.Conclusion:1.Aβ1-42 lateral ventricle injection could imitate the AD inflammatory reaction mechanism; 2.Tianqi Yizhi Granules plays a protective role on the inflammatory reaction in the brain of AD rats by suppressing the activation of glial cells in brain tissues, decreased the expression of phospho-p38/t-p38 and inhibited p38-NF-kappa B signaling pathway activation. Moreover, it can inhibit the expression of COX-2 and iNOS. |
PDF Full Text Request