| Alzheimer's disease (AD) is a degenerative disorder of central nervous system. It is characterized by loss of memory, cognitive decline and misbehavior. Contents of free radicals are increased and metabolic rate is decreased. Major pathological hallmarks of AD are extracellar senile plaques, intracellular neurofibrillary tangles, and drastic neuronal degeneration in many areas involved in cognitive function. Up to now, the exact pathogenesis of AD is not clear. There is no satisfactory therapy for AD.In our experiment, Rhodosin is extracted from medical plants named Rhodiola Sachinonsis A. Bor. There're evidences of its anti-anoxia, anti-cold, anti-fatigue, and anti-toxin, et al. Although many reports had shown its anti-aging, few experiments have made to make out if it has the therapeutic effects on AD. Another medicine used is Melatonin, a biogenic amine with structural similarities to serotonin. Melatonin exerts its regulatory roles though high-affinity, pertussis toxin-sensitive, G-protein(or guanine nucleotide binding protein) coupled receptors. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease such as Alzheimer's disease. We intended to use aging rats to establish a more definite and stable animal model. A (3 was injected into two sides of hippocampus of aging rats induced by D-galactose(50mg/Kg,6w,ip), followed by intraperitoneal injection of Rodosin and Melatonin to observe the behavior, contents of free radicals, capacity of cholinesterase and pathological changes in brain.The wistar rats were randomly divided into 5 guoups: 0.9% NaCl was intraperitoneal injected in the first group of rats(Cgroup), and then Rhodosin(R group), Melatonin(M group) and Rhodosin+Melatonin(RM group) were intraperitoneal injected in the third ,the fourth and the fifth group, respectively. D-galactose was intraperitoneally injected in 2-5 groups of rats, and then 0.9% NaCl(C group) was injected into hippocampus, and A β was injected into hippocampus of the 2-5 groups, respectively. The learning ability on Y-maze test, and the memory ability on one step through test were observed. The activity of SOD, the content of MDA and the viscous coefficient of mitochondrial membrane in hippocampus, the activity of cholinesterase (CHE) and the content of lipofuscin in central cortex were determined. Morphological features were also observed by TEM.The results were as follows: l.behavial effect: Rat's learning and memory ability in C, R, M or RM group were better than in D group. 2.activity of CHE: The activity of CHE in C, M or RM group of rats was increased than that in D group of rats, and there's no significant difference between R and D group. 3.content of lipofuscin: Contents of lipofuscin were decreased in C, R, M or RM group of rats as compared with D group. 4.activity of SOD, content of MDA and viscous coefficient of mitochondria membrane in hippocampus: The activity of SOD, the content of MDA and the viscous coefficient of mitochondria membrane were decreased in C, R, M or RM group of rats as compared with D group. The decrease is coincided with the increase of the ability of learning and memory. 5.pathologic changes on the electron microscopic level: Morphological features of apoptosis inhippocampus neurons could be observed in D group of rats, butnot in control and other ones.This study indicated that intraperitoneal injection of Rodosin, Melatonin or both of them could improve learning and memory deficits in rats with AD and reduced the increase in the activity of SOD, the content of MDA, the viscous coefficient in hippocampus and the content of lipofuscin to their normal levels,and it also showed the protective effects against apoptosis. Melatonin, but not Rhodosin, can improve the activity of ChE. Our results indicated that Rhodosin and Melatonin could markedly inhabit the neurotoxicity of A $ in t... |
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