Proposition And Preliminary Verification Of Emotional Hiddenpathogen Doctrine(EHPD): Impact Of Maternal Rats With Liver-Qi Lack Of Abreaction Before Pregnancy On The Behavior And Neurobiology Of Male Offsprings

Purpose: Hidden-pathogen theory(HPT) is always a leading theory of febrile disease etiology from a proposal to the Ming Dynasty and play a critical guiding role on development and maturity of febrile disease theory. However, with changing times, disease drift, the theory is facing unprecedented challenges, gradually increasing clinical experiences and facts have been difficult to explain and induce using already existing hidden-pathogen theory. Since HPT has its own theoretical status and value and can not be lightly given up, then how to develop this theory in order to better reveal the pathogenesis, guide the diagnosis and treatment becomes the focus of attention. This thesis tries to propose “Emotional Hidden-pathogen(EHP)” as a example to provide a possible paradigm to develop HPT and systematically expound the main ideas and reasoning processes of emotional hidden-pathogen doctrine(EHPD) and to explore its theoretical significance and application value.Method: The issues related to EHPD have been explored adopting literature review and animal experiments combination methods.(1)HPT origins were reviewed in the thesis firstly, then several cinical facts and experiences beyond the exsiting HPT covered areas were summarized and EHPD was proposed to explain and generalize phenomenon mentioned above. EHP operational definition was given and EHPD basic theoretical features were defined and the necessary internal self-consistancy and external compatibility test were conducted.(2)Aimed to the hot scientific issues that the innate hidden-pathogen in EHP affecting offspring emotional diseases pathogenesis, the socialdefeat stress was adopted to induce maternal rats with Liver-Qi Lack of abreaction before pregnancy, the behavioral and neurobiological alrernation of adult male progeny were observed, and the Chinese formula regulating liver was used to interfere on maternal rats mentioned above, the drug impact on the behavioral and neurobiological alrernation of adult male progeny was also investigated. The initial occurrence mechanism of EHPD impacting liver failure catharsis resulting in emotional abnormalities and probable action mechanism of Chinese formula regulating liver were expected to be discovered. The working hypothesis “concerned anxious depression, emotional injury, pathogen hidden in vivo, and pass to offspring” was put forward and EHPD main contents were partially validated.Results:(1)EHP was defined as a class of pathogens outbreaking when confronted with predisposing factors and mainly for emotional abnormalities, including the innate hidden-pathogen and the acquired hidden-pathogen. EHPD was defined as a theory about exploring EHP occurence and development regularity and summarizing diagnosis and treatment experience. The main points included: EHP were got from congenital fetotoxic inherited from their parents, or emotional injury by itself; Common symptoms mainly for emotional abnormalities, and congenital or acquired emotional injury case history was often reported; When the disease did not attack, as normal and mainly for the original disease symptoms when the disease onset; Whether outbreak or not mainly depended on whether vital Qi is abundant; Treatment on the diseases resulting from EHP does not follow the so-called reason therapy, and nonspecific system intervention, particularly focused on early systemic intervention.(2)Animal experiments showed that social defeat applied chronically in maternal rats induces a broad spectrum of behavioural changes that are considered important analogues of depressive symptoms(i.e. Liver-Qi depression syndrome) in humans; After suffering from chronic social defeat stress, maternal rats with liver failure catharsis passed the Liver-Qi depression “symptoms” such as anxiety-like and depression-like behavior and cognitive impairment to their offsprings, and applying the therapy of dispersing stagnated liver qi for relieving qi stagnation to the maternal rats could improve and reverse abnormal behavioral change of parent and offspring; Offspring behavioral abnormalities mentioned above might involve the cascade transduction pathways change of HPA axis hormones, monoaminergic systems and CREB, BDNF transcription factors, and there was evidence that the maternal rats exposed to social defeat stress had the same physiological and biochemical changes, showing the behavioralphenotype and neurobiochemical profile homology of parent and offspring.Conclusions: EHPD operational definition and basic theoretical features were proposed, and necessary logic tests proved the internal self-consistency and external compatibility with the modern Western medicine theory. Based on the theoretical construction, animal experiments methods were applied to explore the pathogenesis of the innate hidden-pathogen impact on offspring emotional diseases. The working hypothesis “concerned anxious depression, emotional injury, pathogen hidden in vivo, and pass to offspring” was proposed and EHPD main contents were partially validated. All of these evidences had proven that EHPD had sufficient and necessary experimental support. After logic and experimental tests, EHPD could be considered as tenable and acceptable scientific hypothesis. EHPD proposal and verification enriched and deepened the existing theory, it is really a initial attempt to develop the traditional Chinese medicine theory. And more, EHPD developing and re-engineering the HPT would definitely have to contribute to enhance the clinical diagnosis and treatment.