Compound Chinese Medicine For The Elderly Cognitive Impairment Beta Amyloid Protein Oxidative Stress And Brain Tissue Of Rats And The Impact Of The Tau Protein Expression

Alzheimer’s disease is a kind of central nervous system degenerative diseases characterized by cognitive decrease. With the aging of population and rising incidence of AD, the pathogenesis of AD and ideal drugs are still a big problem of world medicine.Traditional Chinese medicine based on syndrome differentiation and treatment, with characteristics of chinese herbal compound in multi-target, multi-link, is on the good prospect in prevention and treatment of AD. Huannao Yicong Fang(HNYCF) based on "Deficiency, Blood, Stasis, Turbidity, Toxin" the pathogenesis of AD in TCM, composed of reinforcing kidney replenishing qi and activating blood detoxification Chinese medicine, has been proved good preventive and therapeutic effect of AD in early experimental study and clinical trial.Now we choose natural aging rats for AD experimental model, use modern technology preparation—HNYCF granules, observe the effect on AD animal model in oxidative stress and expression of TTBK1and β-amyloid protein, discusse the mechanism of anti-aging and oxidative stress, so as to provide pharmacological basis to clinical treatment.Purpose:To observe ethology, pathological morphology, oxidative stress and expression of TTBK1and β-amyloid protein of natural aging rats with cognitive impairment after using reinforcing kidney replenishing qi and activating blood detoxification Chinese medicine—HNYCF granules and study its mechanism to AD animal model,so as to provide pharmacological basis to early treatment by TCM.Methods:6018-20months-old aged rats (Sprague Dawley, SD) are used in this study, according to results of Morris water maze and combining with weight, which were randomly divided into aged control group, aged model group, western medicine control group (donepezil hydrochloride,0.49mg/kg), HNYCF granules (produced by Beijing university of traditional Chinese medicine,3.54g crude drug/kg) small dose group (3.78g crude drug/kg), middle dose group (7.56g crude drug/kg), big dose group (18.90g crude drug/kg). The other set104months-old youth SD rats for yang control group. Aged control group, aged model group and yang control group were given to same volume distilled water by gavage. The amount of oral administration was1ml/100g,14weeks duration.After treatment,to test learning and memory capacity by Morris water maze.After intraperitoneal anesthesia (10%chloral hydrate,0.6ml/100g),to draw blood from abdominal aorta, randomly take5brain(hippocampus) homogenate, determinate SOD, MDA, CAT, T-AOC, GSH, GSH-PX oxidatie stress index content in serum and hippocampus organization.Other5rats brain organization fixed by10%neutral formaldehyde solution,to observe morphological changes of hippocampal organization CA1region under light microscopy after HE staining; To observe amyloid deposition changes of hippocampal organization CA1region under light microscopy after Congo red staining; To detect expression of PS-1,β-amyloid protein and TTBK1in hippocampus organization CA1region by immunohistochemical method(color image processing system half quantitative analysis).Results:1. The results of Morris water maze show that both HNYCF and donepezil hydrochloride can improve memory function of natural aging rats with cognitive impairment. Comparing to aged model group, TCM big dose group can significantly increase swimming time and distance in the fourth quadrant(P<0.05, P<0.01).2. HE staining shows that the rats with cognitive impairment hippocampus cell structure are fuzzy, sparsely arranged, shrinkage of some cells bodies and nuclei become pyknotic and hyperchromatic. HNYCF group significantly reduce lesions. Congo red staining shows that there is a lot of β-amyloid protein deposition in the hippocampus of rats with cognitive impairment, which have sizes, uneven colouring. After treatment by HNYCF, aged rats hippocampus still have some shallow orange staining deposition, comparing to aged model group, its number decreases significantly.3. The results of oxidative stress in serum and hippocampus organization show that comparing to aged model group, HNYCF group and donepezil hydrochloride group can significantly improve SOD activity and dicrease MDA content (P<0.05, P<0.01); HNYCF small and big dose group can significantly improve CAT and GSH activity (P<0.01); HNYCF group and donepezil hydrochloride group can significantly decrease β-amyloid protein content in hippocampus (P<0.05, P<0.01).HNYCF small and big group can improve T-AOC in serum and hippocampus, but comparing to aged model group, the statistics is insignificant (P>0.05); HNYCF middle and big group can improve GSH-PX activity in serum, but comparing to aged model group, the statistics is insignificant (P>0.05)4. The results of immunohistochemical half quantitative method shows that the expression of PS-1, TTBK1andβ-amyloid protein are significantly increase in hippocampus CA1area of aged model group. After treatment by HNYCF, the expression of PS-1, TTBK1and β-amyloid proteins are significantly decrease. Comparing to aged model group, the results of IOD decrease significantly(P<0.05, P<0.01).Conclusion: 1. Learning and memory capacity and spatial recognition of aged rats with cognitive impairment decrease. Hippocampus CA1area appears some pathological changes such as shrinkage of some cells bodies and pyknotic and hyperchromaticnuclei, Aβ amyloid deposition increase. The expression of TTBK1, PS-1and P-amyloid proteins significantly increase. Antioxidant capacity in serum and organization and scavenging function of oxygen free radical decrease.2. HNYCF granules can improve learning and memory function of aged rats with cognitive impairment, protect brain Hippocampus organization, improve antioxidant capacity in serum and brain organization, improve SOD, CAT, GSH activity, enhance T-AOC ability, and decrease MDA andβ-amyloid protein content.3. HNYCF granules can improve learning and memory capacity, antioxidant capacity and have anti-aging effect. The mechanism is mainly about improvement of antioxidant capacity, inhibition of MDA and β-AP formation, improvement of brain organization pathological morphology, inhibition of deposits of(3-amyloid protein and TTBK1in brain organization.