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The Oxidative Stress and Anti-aging Function in Chinese Herbal Compound Intervention of D-galactose Induced Mild Cognitive Impairment Rat Model

Author: PuZhiZuo
Tutor: LiHao
School: Beijing University of Traditional Chinese Medicine
Keywords: Chinese herbal compound Cognitive impair ment Bloodlipids Oxidative stress Alzheimer’s disease
CLC: R749.16
Type: Master's thesis
Year: 2012
Downloads: 69
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Objective:The application of the D-galactose combined with a high fat diet composite factors to the production of animal models of cognitive dysfunction in rats, To explore the cognitive dysfunction in rats with aging and oxidative stress index relationship and change.Observation of Huannao Yicong Decoction on by composite factors of cognitive impairment of learning and memory in rats, brain tissue pathological morphology, anti-aging and indices of oxidative stress effect.Methods:Totally60SD rats of clean grade were randomly divided into6groups,the normal group(10rats),the model group(11rats),the Hydrochloric donepezil group(10rats),the low-dose Huannao Yicong Fang group(10rats),The middle dose Huannao Yicong Fang group(10rats),the high-dose Huannao Yicong Fang group(11rats).The model group and treatment group using the D-galactose neck subcutaneous injection of the joint Semi-high-fat diet modeling.The fifth week of the experiment began weighing Rat body weight and intragastric administration. Normal group, model group ig equal volume of distilled water,The other groups were given donepezil hydrochloride (0.45mg/kg, namely9ml/kg the body weight of rats),HuanNao YiCong Fang small doses (3.78g/kg, clinical equivalent dose),HuanNao YiCong Fang middle dose (7.56g/kg,2times the clinical dose equivalent) and HuanNao Fang YiCong large doses (18.9g/kg, five times the clinical dose equivalent).intragastric administration of the drug groups, once daily for consecutive8weeks.All the rats drugs end Parallel Morris water maze test, draw blood from abdominal aorta and centrifuged, supernatant, by a colorimetric method Serum SOD、MDA、CAT、T-CHE、GSH、MAO、NO、NEFA。 The rats were decapitated take the left side of brain tissue, brain tissue stained with HE and observed under light microscope changes of rat hippocampal neurons. The right side of the brain tissue isolated from the hippocampus and cortex, hippocampal homogenate after centrifugation to colorimetric determination of hippocampal tissue in SOD, MDA, CAT, T-AOC, GSH-pX, GSH, T-CHE, NO, MAO, NEFA, biuret method for determination of hippocampal tissue in Tp, NEFA protein content.The right side of the brain tissue separation of the hippocampus and cortex, hippocampal homogenate centrifugation Determination of the SOD in the hippocampus, MDA,biuret determination of the hippocampus in Tp, NEFA protein content.Results: The results of the Morris water maze, the animal model compared with the sham operation group, model group were the first time wearing a significantly longer (P<0.01) reduction in the number of wear Taiwan. With the the model the group after taking Huannao Yicong decoction, Chinese medicine, low-dose group the first time to wear the sets of time significantly shorter (P<0.01or P<0.05), the high-a dose Huannao Yicong Fang group, The middle dose Huannao Yicong Fang group wear the sets the number of significantly increased (P<0.05).Pathological morphology of the rat brain tissue showed that the animal model, the cells of the hippocampal CAl region were sparse, arranged irregularly, occasional cell degeneration and necrosis, visible nucleus hyperchromatic and pyknotic; drug treatment for8weeks compared with the model rats, the administration of each group of hippocampal CAl neurons arranged in more compact and tidy, clear nucleus and cytoplasm, less vacuolar degeneration and necrosis, especially The middle dose Huannao Yicong Fang group form a better.Lipid levels results show that the animal model, the total cholesterol (TG), triglycerides (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly increased (P <0.01) were significantly different compared with the sham; administration of traditional Chinese medicine each dose group and the hydrochloride donepezil group TC and TG levels were significantly reduced compared with model group, the difference was statistically significant (P<0.01or P<0.05). The oxidative stress indicators show that the animal model, rat serum and tissue SOD levels to reduce the level of MDA was significantly higher compared with model group, significant differences (P<0.05); taking the drug, compared with model group, traditional Chinese medicine each dose group SOD levels were significantly increased (P<0.05or P <0.01), MDA levels of traditional Chinese medicine in each group to reduce. Compared with the sham operation group, model group, serum and hippocampus CAT content decreased slightly, the difference was not statistically significant. After administration, compared with model group, Chinese medicine dose group, serum CAT content increased slightly, hippocampus CAT were significantly increased (P<0.01).Determination of anti-aging indicators show that, after the model, serum GSH levels and hippocampal tissue T-AOC and GSH-PX levels were significantly reduced compared with the sham significant difference (P<0.01); Compared with model group, each treatment group serum GSH content was significantly increased (P<0.01), brain tissue T-AOC and GSH-PX levels were significantly increased (P<0.01), TCM dose hippocampus GSH levels were significantly increased (P<0.01).After the model, compared with the sham group, the levels of serum and brain tissue MAO and NEFA content was significantly increased (P<0.01); after administration, compared with model group, traditional Chinese medicine group, large group of serum MAO are significantly reduced (P<0.01), Chinese medicine three dose levels of serum NEFA levels were significantly lower (P<0.01).Conclusions:1. D-galactose combined with a semi-high of fat diet of complex factors can cause cognitive dysfunction in rats, showing a significant reduction of learning and memory and spatial cognitive ability in hippocampus morphology showing dementia-like pathological changes.2. Huannao Yicong Fang can significantly improve learning and memory and spatial cognitive ability in D-galactose combined with semi-high of fat diet of induced cognitive dysfunction, has a protective effect in rat brain hippocampal morphology. And can lower cholesterol and triglyceride levels, play a role in regulating lipid metabolism.3. Huannao Yicong Fang can significantly improve the anti-oxidative stress levels of cognitive impairment in rats, brain tissue content of SOD, CAT and SOD level and decrease MDA level. At the same time, Huannao Yicong Fang can significantly improve brain tissue T-AOC and GSH-PX levels, slow down the aging rat brain tissue, the role of aging.4., Huannao Yicong Fang prevention and treatment of cognitive impairment mechanism may be through the improvement of oxidative stress, regulation of blood lipid metabolism, improve aging capacity and protection of brain tissue morphology.

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