Experimental Study On Prevention And Treatment Of Chemical Drugs Induced Alzheimer's Disease With Vitamin E And Tetramethylpyrazine

ObjectiveAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by progressive decline of cognitive abilities. Up to now, no efficiency therapeutic approaches were found in the world wide.Vitamin E (VE), as an important antioxidant, characterized by its cheapness and good security has received more attention from many people. But there is controversy about its effect. Tetramethylpyrazine (TMP) is an active ingredient isolated from a commonly used Chinese herb chuanxiong, which has long been used in China for the treatment of cerebral — vascular diseases such as cerebral thrombosis and cerebral embolism, some investigation shows that it can delay the learning and memory impairment induced by scopolamine, but its mechanism is unclear. We work to investigate the preventative and therapeutic effect of VE and TMP on AD mice induced by D—galactose and sodium nitrite and its mechanism of effect.MethodsBefore experiment, water maze test was performed to screen the qualified mouse. The AD mice model was induced by D — galactose (120mg · kg^-1, i. p) and sodium nitrite (90mg · kg^-1, i. p) daily and inthe meantime the mice received intragastric administration of VE(28, 280IU ? kg"1 ? d'OorTMPClOO^OOmg ? kg"1 ? d"1) to investigate the preventative effect of VE and TMP, it lasts 50 days. After model established, the mice received intragastric administration of VE (28, 280IU ? kg"1 ? d¹)or TMP(100,200mg ? kg"1 ? d"1) to investigate the therapeutic effect of VE and TMP, it lasts 30days.One hour after finished administration of drugs, water maze test was performed to evaluate the effects of D—gal and sodium nitrite and the preventive and therapeutic effects of VE or TMP on the learning and memory ability of the mice. After completion of behavioral test, the ace-tylcholinesterase (AChE) , superoxide dismutase (SOD) activity and mal-onaldehyde (MDA) content in the brain of the mice were measured with biochemical method. THE The remain mice were perfused and fixed, Observe the morphological change in the brain of all groups with HE staining, the expression of (3—AP, NF—kB in the brain was measured with the immunohistochemistry method. Metamorph image analyses system was employed to take on image analyses.Results0VE and TMP preventative effect: Compared with the mice in control group, the mice escape latency prolonged , reduced SOD activity, increased AChE activity and MDA content, the expression of |3—AP, NF— kB in the model group mice (p AP, NF—kB in the brain. But VE don't show therapeutic effect. TMP can treat the learning and memory ability impairment induced by D—gal and sodium nitrite. The mechanism of TMP is probably related to promote the scavenging of the free radicals, reduce AChE activity and the expression of j3 AP, NF —kB in the brain. But TMP don't show preventative effect.