| Objective Our intention is to design a new animal model of Alzheimer's disease(AD), which can more completely mimic the distinctive changes of praxi, pathology and molecularbiology of AD in human ,and is much closer to the complicate etiopathogenisis and pathological change progress of AD. Then we can provide an important and ideal experimental model to study the pathogenesis and pharmacy of AD in the future. Method An animal model of AD was founded by injecting beta-amyloid 1-40 and aluminum into the lateral cerebral ventricle of SD male rats. These rats were divided into three groups, control group (normal saline 4ul,for 14 days), low dose group (beta-amyloid 1-40 2ug, for 14 days and 1%AlCl3 2ul, for 5 days) and high dose group (beta-amyloid 1-40 4ug, for 14 days and 1%AlCl3 3ul, for 5 days). Each group includes 8 rats. All of them were injected 10ng TGFβ1 into the anterodorsal nucleus of thalamus at the first time. After the injection, we detectd the praxiological disorder of rats by morris water maze and shuttle box test one week later. Then we randomly selected 3 rats and stained their brain tissues by HE, Congo red and silver and detected the activity of choline acetyltransferase and beta-amyloid in the brain tissues by immunohistochemistry. After 3 months, we had the experiments of morris water maze, shuttle box test, and stained again for the next 5 rats. Result 1. Praxiological disorder: 1.1 In the morris water maze test, the sample rats' latency of searching for the platform is obviously longer than the control rats (p<0.01).And the latency of high dose group is longer than that of low dose group (p<0.05).The latency of the rats detected 3 months after the experiment is longer than the rats detected one week after that, but there is no statistic significant difference (p>0.05). The times of crossing platform within 120 seconds of sample rats are obviously less than the control ones (p<0.01). 1.2 In the shuttle box test, after one week and 3 months, the electric shock times of low dose group (12±2.39 and 15.4±4.34) and the high dose group (3.63±3.11 and 17.6±2.51) is more than the control group (8.38±1.69 )(p<0.01). The escape response latency of low dose group (51.6±25.05 seconds and 57.6±31.58 seconds) and the high dose group( 57.5±32.99 seconds and 79.6±34.20 seconds) is more than the control group(21.25±6.04 seconds)(p<0.05). Moreover, the electric shock times and the escape response latency detected 3months later are more than that of the rats detected one week later, but there is no significant difference(p>0.05). 2. Histopathological changes of cerebrum: After one week and 3 months, the neurons of sample rats show derangement, karyopyknosis, gliacyte proliferation. The brain tissues of the sample rats are positive when they are stained by Congo red. The nerve fibers of the sample rats are enlarged, engorged, and twisted. Furthermore, we find senile plaques and neurofibrillary tangles in the cortex and hippocampus 3 months later. 3. Biochemical indicator change: 3.1 After one week and 3 months, the number of ChAT in the low dose group ( 12±3.40 and 16.67±4.84) and the high dose group ( 7.50±1.87 and 7.83±2.31) is distinctly decreased than that of control group(p<0.01). The number of positive cells in the high dose group is more markedly decreased than that in the low dose group(p<0.05). And dyeing of the sample rats is lighter. 3.2 After one week and 3 months, a lot of anti-Aβ positive cells can be found in the cortex and hippocampus of the sample rats, and the dyeing is profunda. Compared with the control group(12.67±4.32), the numberof Aβpositive cell body in the low dose group ( 25.67±7.11 and 26.5±6.06) and the high dose group ( 34.5±11.58 and 31.0±10.35) sample rats is visibly increased(p<0.01). Conclusion 1. We founded a new animal model of AD by jointly injecting beta-amyloid 1-40 and 1% AlCl3 into the lateral cerebral ventricle of rats, at the same time injecting 10ng TGFβ1into the anterodoral nucleus of thalamus at the first time. 2.
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