| Alzheimer disease (AD) is a neurodegenerative disease which mainly occurred in old age. The pathologic feature of AD are senile plaques(SP), neuronal loss or degeneration and neurofibrillary tangles(NFT) mainly. The clinical feature of AD are memory impairment, cognitive disorder and neuron functional impairment. With the global acceleration of aging, the incidence of AD becomes an increasing trend. How to prevent AD becomes a popular topic in the life sciences.Objective:1. To research the effects of FA on neurological behavior in mice cerbral neuronal cells induced by KA.2. To research the effects of FA on apoptosis proteins Bcl-2, Bax, Caspase-3, Caspase-9 in mice cerbral neuronal cells induced by KA.3. To study the effects of FA on the reactive astrocytes in mice cerbral neuronal cells induced by KA.4. To study the effect of FA on the activity and apoptosis rate of PC 12 induced by KA. Methods:1. KA was injected into hippocampus of mice to establish model of AD, the mice were given to continual intragastric administration for 30 days. Morris water maze is a particular facility to test the neurological behavior of mice.2. To reseacher the effect of FA on apoptosis proteins Bcl-2, Bax, Caspase-3, Caspase-9 in mice cerbral neuronal cells with Immunohistochemical stainin.3. To reseacher the effect of FA on the reactive astrocytes in mice cerbral neuronal cells with Immunohistochemical stainin.4. To study the effect of FA on the activity of PC 12 induced by KA and the percentage of apoptotic cells with Immunohistochemical stainin and Flow cytometry. Results:1. After 30 days positioning injected KA into hippocampus in mice, the model group of mice had the least times to pass through platform quadrant and swimming path was mess and irregular changes. In the place navigation test, compared with the sham operation control group, the escape latency of the mice in the model group were significantly increased with the increasing number of training days(P<0.01). In the spatial probe test, compared with the sham operation control group, the times of pass through platform of the mice in the model group were significantly decreased (P<0.01) and the duration of pass through quadrant were significantly shortened (P<0.01).30 days later, ferulic acid in the treatment group of mice passed through platform quadrant more and more times. In the place navigation test, compared with the model group, the escape latency of the mice in the FA group were significantly decreased(P<0.05). In the spatial probe test, the FA mice passed through more times and spend more time in the target quadrant than the model group (P<0.05).2. The results of IHC showed that compared with the sham operation control group, the expression of Bcl-2 in AD model and FA groups remarkable increased. The expression of Bcl-2 in high,middle low-dose FA groups were also remarkably increased compared with in model group, it indicate that neuronal cells can inhibitor apoptosis result from KA by overexpression of Bcl-2. Furthermore the expressions of Bax in the AD model group were higher than the sham operation control and FA groups, as a result the ratio of Bax/Bcl-2 remarkable increasted. It thus clear that the ratio of Bax/Bcl-2 determine cell survival or death. In addition, compared with the sham operated group the expression of caspase-3 and caspase-9 in model and FA groups were signifieantly higher and significant increase in neuronal apoptosis, which conjectured that caspase-3 and caspase-9 play an important role in the mechanism of neuronal apoptosis induced by KA.3. Compared with the sham operation control group, the expression of GFAP in AD model and FA groups increased remarkably and mainly located at hippocampus and dentate gyrus, a large number of glial cells activated which would hurt the neuron directly or indirectly. In addition, compared with the sham operation control group, the co-expression of GFAP and IL-1β,the co-expression of GFAP and TNFa in AD model and FA groups increased strikingly, which indicated that cortex astrocytes would be active and at the same time cytokine can enhanced the function of excitotoxicity which involved in AD pathogenesis.4. Cell climbing film by immunohistochemistry and flow cytometry showed that PC 12 cells after injury by KA, compared with the sham operation control group, the quantity of cell decreased significantly in model group, protuberance lost or broken, weakening the link between dendritic cells. The death percentage in the sham operation control group descended significantly while the model group rose.Conclusion:1. The ability of learning and memory of the recession is a important behavioral characteristics in AD. No matter from the escape latency which reflect the ability of obtaining information, or the times to pass through platform and the time spent in the target quardrant which reflect th ability of memory, ferulic acid can improve the ability of learning and memory on mice.2. The apoptosis of brain neuron is a critical feature in AD. The results showed that FA can inhibit apoptosis caused by KA, it's function may be make effort by involving in regulating the expressing of apoptosis proteins Bcl-2, Bax, Caspase-3, Caspase-9 in mice cerbral neuronal cells.3. These remarkable increased of active astrocytes in AD indicated that when the nerve cells are poison, astrocytes appear glial reaction and activated, prompted GFAP lots of synthesis. At the same time, Cytokines IL-1β, TNFa participated immune inflammation, expression significant increased, which reveal the extent of the damage in brain.4. The results showed that ferulic acid obviously improve the PC 12 cells vigor and form, reduce the neurons damage caused by the excitability of nerve toxin and the neuroprotective effect in KA mode. |
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