Experimental Study Of The Mechanism Of Visceral Wen Yang Huayu Decoction On Atherosclerosis In Rats With Vascu Lar Dementia

Vascular dementia(VD),resulting from brain loss caused by varieties of cerebrovascular diseases, is an acquired intelligent damage syndrome and cognitive function defect.Cerebrovascular diseases lead to atherosclerosis, and ischemia or ischemia-reperfusion injury will appear, which results in dementia. In this case, VD animal models,based on atherosclerosis, were made in our research, to highly imitate the pathogenesis of VD.According to "yang transforming qi while yin constituting form" in Chinese traditional medical, atherosclerosis is caused by the inadequacy of yang and yang transforming and the over dose of yin. Therefore,"wu zang wen yang hua yu tang" was applied in the study of atherosclerosis VD. Oxidative stress is probably an important factor of VD. In the experiment, the researcher began with Nrf2/ARE pathway to observe therapeutic the effect of Visceral Wenyang Huayu Decoction on VD and the mechanism.Objective:firs, develope a rat model of VD and observe therapeutic effect of different doses of Visceral Wenyang Huayu Decoction on these rats; second, from the aspect of Nrf2/ARE pathway in oxidative stress, examine the decoction’s defense mechanism against VD nerves.Method:Healthy SD rats with half males and half females were divided randomly into a sedentary control group, a sham-operated group and a model group, and fed on high-fat diet with an intraperitoneal injection of70IU/kg vitamin D3. Then the VD rat models were established by repeatedly cerebral ischemia. Then Morris water maze was applied to testing the memories of rats, HE staining was used to observe their hippocampus.Four weeks later, these rats were divided randomly into a sham-operated group, a sedentary control group, a low-doses group, a middle-dose group, a high-dose group, and a Piracetam treated group. After4weeks’gastric perfusion, their spatial learning and memory function were tested by the Morris water maze. Biochemical detection was used to examine the standards of their SOD, MDA, LPO, GSH-PX, and T-AOC, while western blot to examine the expression of Nrf2protein in the nucleus and cytoplasm, and the expression of HO-1protein. RT-PCR was used to test the expression of HO-1mRNA, and EMS A to combining power between Nrf2and ARE.Result:(1) In the middle-dose group and the high-dose group, the rats’escape latent periods in Morris maze were shortened from the third day on, while in the low-doses group and the Piracetam treated group, no obvious change appeared. In spatial search test, the stay and distance were lengthened, while in low-doses group and the Piracetam treated group there was no significant difference.(2) In the treatment, Visceral Wenyang Huayu Decoction had active effect on the oxidative stress damage in the hippocampus of rats, especially for high-doses and low-dose groups. It could increase GSH-PX. SOD、T-AOC and lower in the hippocampus to protect it from oxidative stress damage.(3) Nrf2/ARE pathway in hippocampus of VD rats were activated. In Western blot test, it was found that Visceral Wenyang Huayu Decoction could transport Nrf2protein from cytoplasm to nucleus. The decoction could also activate HO-1and strengthen its expression, according to RT-PCR test in HO-1mRNA.(4) In the EMS A test, it was showed that the decoction could also strengthen the combining power between Nrf2and ARE.Conclusion:Visceral Wenyang Huayu Decoction can improve the learning and memory ability of VD rats. It may concern the oxidative stress reaction and antioxidant mechanism in VD rats, especially in high-doses and low-dose groups.