| Objective: To study the mechanisms and the effects of Capsule Yi-Zhi (CYZ) on the animal and cellular models of Alzheimer's disease and, at the same time, find out some other pharmacological and texicological data of CYZ. Methods: Two different types of animal models were induced by scopolamine intraperitoneal injection on rats and long term D-galactose subcutaneous injection on mice respectively. Then MORRIS water maze test, step-through test and Y-maze test were performed to explore the changes of the animals' recognition and memory capacity with tests of SOD and MDA level in the mice's blood carried out simultaneously. β amyloid protein fragment 25-35 was added to the primarily cultured SD rats' cortex neurons to produce neurotoxicity and then MTT assay and LDH test of the culture media were employed to detect the protective effects of CYZ on poisoned neurons. Moreover, radioligand binding was introduced to explore the effects of CYZ on M and N receptors in the senile rats' brain cortex, In other experiments, fatigue test, auto-activity examination, experiment of pentobarbital hypnosis and orally administered extremely high dose CYZ were done respectively to obtain the pharmacological and toxicological data of CYZ. Results: CYZ could significantly improve the learning and memory capacity of the rats. In MORRIS water maze test, the mean latent tune for the rats' finding the platform was decreased from 19.5±11.40 seconds to 8.5±2.39, 8.8±3.07 and 7.4 ±3.87 seconds respectively. And in step-though test, compared to the model group, three groups with increasing doses of CYZ got decreased error numbers from 14.20±7.74 to 7.50±8.02, 3.40±4.43 and 2.50±3.10 and the latent time increased from 22.70±23.07 seconds to 148.50±124.02, 176.50±143.36 and 196.60±128.00 seconds. While in Y-maze test, after the long-time galactose treated mice received various doses of CYZ administration, the times needed for their learning test shrank from 31.35±8.97 to 19.67±8.07,14.00±6.84and 11.41±5.99 and those for their memory test also went down from 17.12 ±5.57 to 11.27±6.65, 8.29±5.95 and 6.24±4.97. What's more, the levels of SOD and MDA in the mice's blood were significantly raised from 17.69±3.14mgprot-1 to 26.94±4.46, 19.80±3.78 and 21.33± 3.63mgprot-1 and reduced from 4.08±0.88 mgprot-1 to 2.82±0.75,2.10 ±0.42 and 2.35±0.39mgprot-1 respectively. In primarily cultured rat cortex neurons, CYZ presented satisfactorily protective and therapeutic effects on A β induced neurotoxicity. In MTT assay, compared with control group, the average optical absorption of prevention and treatment groups rose from 0.68±0.193 to 0.93±0.009 and 0.96± 0.239 and the LDH levels in the media correspondingly dropped from 3670.2±437.65U/L to 864.5±371.69 和 1444±635.18U/L. Then in radioligand binding test, after three doses of CYZ administration, the M acetylcholine receptors in the senile rats' brain cortex seemed to be only slightly affected whereas the density of N receptors did rise up significantly from 47.3±9.77 fmol.mg-1 to 62.9±6.35, 89.7±7.82 and 97.2±10.14 fmol.mg-1. Moreover, CYZ could also raise the mice's ability of anti-fatigue, which was indicated in the mice's swimming test that the swimming enduring tune of three groups of mice treated with CYZ rose from 25.1±8.33 minutes to 47.0± 12.78, 57.2±23.26 and 51.6±12.75 minutes respectively. Further more, CYZ could prolong the tune needed for the mice's falling asleep from 210.80±32.91 seconds to 244.40±38.50, 244.20±39.03 and 244.05± 24.72 seconds and shorten the endurance of the sleep from 47.40±13.75 minutes to 32.95±7.67, 41.00±8.06 and 32.65±5.70 minutes after beinghypnotized by pentobarbital. However, CYZ had no obvious influence on the mice's locomotor. No abnormality was seen when mice were treated with high dose of CYZ (7g/kg) orally. Conclusion: CYZ presented protective effects on various experimental models of AD and elevated the animals' ability of anti-fatigue and the excitability of central nervous syst...
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