| BackgroundAlzheimer disease (AD) is a neurodegenerative dementia characterized by neuronal cell loss, senile plaques (SP) , cerebral amyloid angiopathy (CAA) and neurof ibrillary tangles (NFT). These lesions are associated with beta amyloid (A β) deposit ion in vessels and parenchyma in brain of AD patients. Interventing production and metabolism of the Aβ , it can reduce neurotransmitters deficits such as choline acetyltransferase (ChAT) and cognitive impairments probably associated with polymers of Aβ including SP and/or CAA. Therefore, the best therapeutic strategy should be intervention of the production and metabolism of A β via drugs to promote degradation and clearance of these polymers. It is unknown role of Chinese herbal medicine plays in the degradation and clearance of these polymers. For it, we set up the project on research into effects of King's Brain pills, a herbal medicine, on production and metabolism of Aβ, and its polymers in the brain of AD model induced by Aβ injection, based on our previous studies on " role of vascular factors in the pathogenesis of AD " completed in the United Kingdom. ObjectivesIn order to investigate how does King's Brain pill work or mechanism of King's Brain pill effective in treating AD clinically, we observed effects of extract of King's Brain on neuronal and vascular lesions induced by A β combining with praxiology and neuropathology, Materials and Methods12-month-old SD rats were divided into model group (3day, 7day, 14day, 28day), sham group, KB (King's brain) group and Control treat group (14day, 28day) randomly. Except sham group , other groups were injection with condensed A β1-402μ1 (10μg) into rat right hippocampi. KB group were treat with KBO. 7ml/100g after operation 3 days, once a day. Control treat group were treat with Aricept 0. 92mg/KgO. 7ml/100g, once a day. 28 day rat were detected the praxiology by Morris water maze 23 days later lasting 5 day. We made paraffin section after 3 day, 7 day, 14 day and 28 day for all kinds of stain, and detected the brain pathology by HE; and detected the brain and vessel A β deposit ion by Congo Red stain;, and detected the neuron Nissl body by Toluidine blue stain; and observed the ultrastructure of the Hippocampi neuron, nerve fiber, and vessel by transmission electron microscope; and detect A β, βAPP, ChAT, S100β, Bcl-2,Bax and Synaptophysin with SABC and pAPPmRNA expression with in situ hybridization. To analysis these protein and β APPmRNA expression with MetaMorph image analysis system at hippocampi and cortex lesion regions. Results4. 1 The learning and memory function of model rat which were induced by A β were impaired. Their neuron and vessel at the right hippocampi and cortex were injured seriously, and their related gene expression were coincidence with AD clinical feature.4.2 Result of Morris water maze praxiology suggest that the total incubation period (sec) and total average swim distance (cm) and incubation period (sec) and average swim distance (cm) in each quadrant of the KB group were significantly shorter than model group at the 2nd and the last training (P<0.05 or P<0.01 ) , and no different with sham group (p>0. 05 ) , and equivalent with Control treat group (P>0. 05) .4.3 The result of neuropathology suggest that neuron and vascular lesion of KB group induced by Aβ were ameliorated significantly. The result of transmission electron microscope suggest KB group nerve fiber damage were ameliorated significantly, and the inflammation response induced by A β were relieved significantly. The result of immunohistochemistry and image analysis suggest that KB group at 28day the A β deposition Optical density Total and AREA total at hippocampi and cortex lesion regions were significantly lower than Model group at the same regions (P<0.05 or P<0.01 ) , and no different with normal group (p>0. 05) KB group at 28day the A P deposit ion Optical density Total at vessel were significantly lower than Model group at the same regions(P<0.05) , and no different w...
|
PDF Full Text Request