Study On The Mechanism Of Lung Warming And Turbid Descending Decoration Of TCM Fu-Yang School In The Treatment Of Vascular Dementia

Vascular dementia is caused by brain damages due to cerebrovascular dise ases. With dysfunctions of memory, attention, language, executive function and other higher cognition function as main clinical manifestations, vascular demen tia(VD) is the second most common form of dementia after Alzheimer disease(AD). In China, the incidence of VD increased year by year and become a h eavy burden to the families and society. Specific pathogenesis of vascular deme ntia is not yet clear. While modern medicine is lack of effective treatment, Tra ditional Chinese Medicine(TCM) showing the superiority in the prevention and treatment of VD.The TCM Fu Yang School inherited the yang-oriented thought of Huangdi Neijing, the Internal Canon of Medicine, and attaches great importance to the role of Yang in human physiology and pathology. Theoretical core of which i s the Yang dominant and Yin subordinates. The treatment follow the rule that when the Yang aspect is ill, Strengthening Yang and suppressing Yin, while re solve Yin with Yang when Yin aspect is ill. Professor Tang Nong of Fu Yang School proposed the treatment of VD with the method of warming the lung a nd descending the turbid. Through experiment and clinical verification this met hod has shown a good prospect.The latest research shows neural cell apoptosis together with neurotrophic factors involved in the pathophysiological process of VD, and closely related to the neurotrophic factor pathway(BDNF / Tr Kb-P38 / MAPKAPK2-CREB). T herefore, this study detects the impact of VD on learning and memory of rats by copying vascular dementia rats and Morris water maze test. Observed the a poptosis of CA1 pyramidal cells with HE staining, TUNEL method and electron microscopy. Detect the m RNA and protein expression of neurotrophic factor pathway(BDNF / Tr Kb-P38 / MAPKAPK2-CREB) with immunohistochemistry,RT-PCR and Western Blot to explore the effector mechanisms of Lung Warm ing and Turbid Descending Decotion in the intervention of VD. For this reason,the paper expands research from the following two aspects.1. TCM Theoretical StudyFirst of all, analyze the understandings of VD in TCM classics and classic works of ancient physicians, and the current research status of VD TCM treat ment. Secondly, reductively interprets the core theories and methods of TCM F u-Yang School by combining the meticulous combing the heritage context of T CM Fu-Yang School, TCM classics, and the theory of Yin-yang ontological str ucture of human body proposed Professor Tang Nong. Reveal the Yin-yang ont ological structure theory of human body from the perspective of Tai and Pi he xagrams of The Book of Change. Clarify the essence and use relation(Ti Yong)of Yin and Yang. Elucidate the profound connotation and denotation of the Y ang dominant and Yin subordinate Theory. Interpret the body’s self-healing mec hanism. Combine with practice, detailed analysis the close relationship between the basic Therapeutic Principles of Strengthening Yang with the Zhong Tu or spleen and stomach. Clarify the Deficiency- Cold nature of three yin disease of Treatise on Febril Disease and its therapeutic principles. Finally, put forwar d VD belongs to three Yin disease from the perspective of Fu Yang school th eory. The root cause of its pathogenesis is Yuan Yang decline, vital activity(Shenji) disused and the outward symptoms is the Lungs failure to declared d own, phlegm and blood stasis in the brain. Pursuant to which proposed warm t he lung and Descending Turbid decoction, treatment sequentially according to t he order of pathogenesis and attach a clinical medical case.2. Experimental ResearchObjective: Establish a rat model of VD, to observe the influence of Warm ing Lung and Descending Turbid Decoction on the learning ability of memoryin VD rats with the pathological changes of hippocampus and neurotrophic fact or pathway(BDNF/Tr Kb-P38/MAPKAPK2-CREB). And to explore the intervent ion mechanisms of Lung Warming and Turbid Descending Decotion on VD.Method:select healthy male SPF class SD rats, after adaptive feeding, reject extre me values with Morris water maze test. The rats were randomly divided into c ontrol group and model group, with bilateral carotid artery occlusion and reperf usion animal model making method. After the wound healing of rats, followed by a second Morris water maze test to screen for successful modeling rats. R andomly divided into 5 groups, respectively: model group, low dose Chinese m edicine group, Middle dose Chinese medicine group, high dose Chinese medi cine group, and western medicine group. Continuous administration for 28 days,then carry out the third Morris water maze test, and then extract material.Use the HE staining, TUNEL assay and electron microscopy methods to o bserve the morphological changes in neuronal tissue, analyze the impact of Lun g Warming and Turbid Descending Decotion on the pathological changes in th e hippocampus of VD rats.Using immunohistochemistry, RT-PCR, Western Blot to test the m RNA an d protein expression of neurotrophic factor pathway(BDNF / Tr Kb-P38 / MAP KAPK2-CREB) detection, Analyzing the impact of Lung Warming and Turbid Descending Decoration on this neurotrophic factor pathway.Result:The learning and memory ability of the rats in the model group significan tly damaged in Morris water maze test, and learning, memory ability of rats h ave significantly improved under the intervention of Lung Warming and Turbid Descending Decoration, and treatment effect of the high-dose group of Chines e medicine is the most significant.He staining, TUNEL and electron microscopy results showed that compare d with the model group, the hippocampal neurons morphology in rats of the Lung Warming and Turbid Descending Decoration groups were improved to diff erent degrees; and the treatment effect of high-dose group of Chinese medicine is the most significant.Immunohistochemistry, RT-PCR, Western Blot results showed that compare with the model group, the BDNF, Tr KB, CREB protein and m RNA expressi on the hippocampal CA1 region were increased, and the p38, MAPKAPK2 m R NA and protein expression were decreased in the three groups of the Lung W arming and Turbid Descending Decoration. And the effect of high dose treatme nt group is the most significant.Conclusion:Results of variety of experimental shows that the Lung Warming and Turb id Descending Decoration had significant improvement the learning and memor y of VD rats, Significantly inhibited the hippocampus neuronal apoptosis, ther eby protecting neurons. The prevention and treatment of vascular dementia may be possible to regulate the survival of nerve cells through a dual mechanism:BDNF-induced phosphorylation of p38 / MAPKAPK2 signaling pathway and i nhibiting its pro-apoptotic function; to induce the expression of pro-survival ge ne by CREB way. In turn, the activity of neurons can be induced expression of BDNF by CREB-dependent mechanism forming a circulation path between BDNF and CREB.