The Mechanism Of Treatment Of Tongxinluo On Learning And Memory Ability Of SAMP8

AD is an incurable progressive degenerative disorder of the central nervous system. Its typical pathological characteristics are senile plaques deposits and neurofibrillary tangles in Cerebral Cortex and Hippocampus. TXL was developed as compound Chinese Medicine, based on the Collateral Theory. Recently, clinical research that TXL had some effect on AD, but its mechanism is not clear. Senescence accelerated mice P8 has typical AD neuropathology biochemical and pathological feature. So, SAMP8 is ideal model of early AD pathogenesis research.To explored whether TXL treatment can improve early AD Pathological changes and their learning and memory abilities, as well as the related mechanisms, SAMP8 was chioced as study objects in this thesis that consisted of four parts.Part one:Exploring the effect of the TXL treatment on learning and memory ability of young SAMP8 mice. Four months old SAMP8 mice were treated by different doses of TXL. Meanwhile, four months old SAMR1 and HuperzineA treated mice were choiced as normal control and positive control, respectively. At the end of fourth week and eighth week, we used step down test analysis system and Morris water maze test analysis system to detect changes in learning and memory abilities of mice, respectively. The results showed that, to some extent, TXL treatment could improve learning and memory ability of early stage SAMP8.Part two:Exploring the effect of TXL treatment on changes of neurons shape and proliferation of astrocytes in young SAMP8 mice brain. After 10 weeks of TXL administration, morphological changes was detect such as neurons chromatin aggregation by HE staining. GFAP level of mice brain was detected by to evaluate inhibition of inflammatory response in SAMP8 mice brain by TXL treatment. The results showed that, to some extent, TXL could improve the SAMP8 brain neuronal morphology, while inhibition of inflammatory response in SAMP8 brain by TXL was not significant.Part three:Exploring the effect of TXL treatment on amyloid Pathological changes on the SAMP8 mice brain. After 10 weeks of TXL administration, glycogen and Amyloid deposition in mice brain were detected by PAS stainingn and Congo red staining, respectively; Aβ42 oligomers levels andβ-amyloid precursor protein in mice brain were detected by immunohistochemistry staining. The results showed that:In a way, TXL treatment could improve the hippocampus glycogen deposition, reduce brain amyloid lesions, reduce the level of Aβ42 oligomers, and reduce APP expression in Hippocampus, which indicated TXL treatment could alleviate the Aβtoxic.Part four:Exploring the effect of TXL treatment on pro-apoptosis protein in SAMP8 mice brain. After 10 weeks of TXL administration, pro-apoptotic protein Caspase-3 and bax levels in mice brain were detected by Western blotting. The results showed that:with the increase of TXL dose, pro-apoptotic protein Caspase-3 levels in SAMP8 mouse brain were decreased, however, the bax protein did not been decreased.Conlusion:To some degree, TXL can improve learning and memory capability of four months age SAMP8. We speculated that the related mechanism maybe achieved by reducing level of Aβ42 oligomers, reducing the expression of hippocampal APP, reducing glycogen deposition in the hippocampus, alleviating brain amyloid lesions and decreasing the Caspase-3 expression in mice brain. These results will provide an important experimental basis for TXL treatment on early lesions of AD。...