| It is a kind of disease which we call it endometriosis shortened as EMs that the endometrial tissue consisting of glands and stroma with the ability of growth appears outside of the womb cavity mucous membrane. EMs presents with abdominal pain, dysmenorrhea, sexual intercourse discomfort and infecund etc as typical symptoms. Although EMs is a benign disease, it has the ability of distant metastasis and planting growth as malignant tumor. About 3%～10% women in reproductive age suffer from EMs. About 25%～35% patients with infertility,20%～90% patients with chronic pelvic pain and 40%～60% patients with dysmenorrheal suffer from EMs. EMs is a kind of common and frequently-occurring gynaecologic disease. It has a great effect upon women life quality. In recent years, the incidence of EMs is gradually increasing and the relapse rate is still very high after treatment. Traditional Chinese Medicine have good effects on the EMs, which can improve symptoms, raising pregnancy rate, lowering relapse rate and regulating immunity.In the seizures of EMs, immunology theory is a popular research. Because organic immune balance is broken, ectopic endometrium can escape from the monitoring of immunization, then plant and grow into the lesion site. Immune related cytokines played an important role in this process. At present, the autoimmunity-associated cytokine studies show that immune related cytokines not only indirectly reflect the immune status of organism, hypothesizing the immune environment on the occurrence and development of EMs, but also are involved in the development of EMs links.According to Traditional Chinese Medicine, the basic pathogenesis of EMs is blood stasis. In addition, many other pathogenesis, such as qi stagnation, cold coagulation, kidney deficiency, phlegm and so on, are related with EMs as well. Among early EMs patients, blood stasis, qi stagnation and cold coagulation are in large proportion. At present, the thought about Traditional Chinese Medicine and Modern Medicine believe that the disorders of the immune system can be caused by blood stasis, qi stagnation and cold coagulation. Besides that stagnation of qi is involved in the regulation of central monoamine neurotransmitters.Ben Shi Hu Po San (BSHPS) comes from "Pu Ji Ben Shi Fang", which was written by Xu Shuwei in Song Dynasty. BSHPS is formed by Triangular, Turmeric, Red peony root, Liu Ji Merino, Paeonol, Cinnamon, Radix, Angelica, Radix Linderae and Corydalis tuber. BSHPS has the effect on operating qi, activating blood circulation, warming meridian and relieving pain. It is mainly used in the treatment of women with dysmenorrhea in ancient time. Now it's often used to treat gynecological disease, main symptoms of which are dysmenorrhea or infertility and so on. At present, there are a number of research reports about the use of BSHPS in the treatment of EMs, but the focus is more concentrated on the clinical efficacy observation and the use of rules, lack of basic research.Based on the above basis, we think that, as a basic method of treating EMs, BSHPS may have regulation effect on the immune cytokines which play an important role in the development of EMs. The three different functions, operating qi, activating blood circulation and warming meridian may have different meanings in regulation. At the same time, as the characteristic sign of qi stagnation, central monoamine neurotransmitters may also be regulated by BSHPS. Therefore we design this research around the above problems.The research content is divided into 3 parts:Part one is about the effects of BSHPS and its decompositions on the Thl/Th2 cells drift in EMs model rats. We discuss about the mechanisms of BSHPS and its decompositions for regulating Thl/Th2 drift in endometriosis, by comparing the levels of IFN-γ, IL2, IL-4 and IL-10, which are characteristic cytokines secreted by Thl and Th2 cells, in endometriosis model rats before and after using BSHPS and its decompositions. Part two is about the effects of BSHPS and its decompositions on immune cell factors. If ectopic endometriums want to survive at abdominal wall, they must experience "Attachment-Aggression-Angiogenesis" which is shorten for "3A model". Arrounding the "3A model", targeting to cytokines which are related to immunity, ectopic endometrium invasion of basement membrane and angiogenesis, we explore the mechanisms of BSHPS and its decompositions for preventing and treating EMs. Part three is about the regulation function of BSHPS and its decompositions on central monoamine neurotransmitter. Observating the effection of BSHPS and its decompositions on hypothalamus monoamine neurotransmitter and its metabolites, we explore the treatment mechanism of BSHPS and its decompositions for qi stagnancy and blood stasis. The experimental results and conclusions are as follows:1. BSHPS and its decompositions have effects on inhibiting the Th1/Th2 cell drift in EMs rats peripheral blood.The phenomenon of Th1/Th2 drift can reflect the immune status of body. As the characteristics cytokines that Thl cell and Th2 cell secreted, the ratio of IFN-y/IL-4 is an important index to measure the balance of Th1/Th2. BSHPS inhibits the Th1/Th2 drift, adjusts the immune function of body and plays a role in preventing and treating EMs, just by modulating IFN-γ/IL-4 ratio. Among above, the drug combination which has the function of activating blood circulation, has the best effect in regulating the ratio of IFN-γ/IL-4.The drug combination which has the function of operating qi can reduce the content of IFN-γ. And the drug combination which has the function of warming meridian and enriching the blood has an obvious effect on increasing the content of IL-2. The drug combination which has greater effect on activating blood circulation than operating qi, can significantly increase the content of IL-10. But if the function of operating qi increases, the effect of the drug will go to the other side.2. BSHPS and its decompositions have effects on immune cytokines in the peripheral blood and endometrial changes of EMs rats.BSHPS can reduce the elevated trend of TNF-α, IL-6 and MIF in the peripheral blood of EMs rat, and also can significantly reduce MMP-2, TIMP-2 and VEGF levels in the ectopic endometrium. It illustrates that improvement of immunity, inhibition of ectopic endometrial planting and invasion, and angiogenesis may be the mechanisms of BSHPS in treating EMs. Content of TNF-αand IL-6 in the peripheral blood have consistent changes by using BSHPS in spliting and synergy groups. That means TNF-αand IL-6 have correlation. BSHPS and its decompositions may influence the content of IL-6 by regulating the content of TNF-α. The study of decompositions finds that operating qi, activating blood circulation and warming meridian and enriching the blood can separately inhibit the ectopic endometrial invasion and angiogenesis in EMs. The combination of operating qi and activating blood will promote the planting and invasion of ectopic endometrium, and must be combined with warming meridian and enriching the blood medicine in order to play an obvious role of treating EMs.3. BSHPS and its decompositions have effects on hypothalamic monoamines neurotransmitter of EMs rats.The changes of monoamine neurotransmitters in hypothalamus is microcosmic performance of liver-qi stagnation syndrome, which manifests the decrease of NE content and enhanced activity of 5-HT, DA. BSHPS can increase the ability of hypothalamic NE,5-HT and DA content, but inhibite 5-HT and DA activity, which may be one of the mechanism on treating qi stagnation and blood stasis type EMs. At the same time, the research of decompositions also finds that components of operating qi and activating blood significantly increase the NE,5-HT content on the hypothalamus. The components of activating blood can reduce 5-HIAA and HVA levels. These indicates that the functions operating qi and activating blood can increase the content of monoamine neurotransmitters in hypothalamus and inhibit its activity. It is by the function of operating qi and activating blood that BSHPS is successfully applied to treat the syndrome of liver-qi stagnation.Besides, the study finds that the Th1/Th2 mainly manifest Th2 cells drift toward THl cells on EMs rats. That Thl cells drift toward Th2 cells shows the immune inhibitatory status, while Th2 cells drift toward Th1 cells shows the immune activated status. On patients with EMs, the ectopic endometrium escape from the monitoring of immunization, then plant and grow outside cavity of uterus due to hypoimmunity. There is not the condition of hypoimmunity on the autologous endometrium transplantation model of rats, but the ectopic endometrium planting activates the immunity system, then it manifests that Th1 cells increase and Th2 cells reduce or the ratio of Thl/Th2 increases.At the same time, there is also the tendency of stagnation in the autologous endometrium transplantation EMs model of rats, namely 5-HT and DA activity increases. Blood stasis is the basic pathogenesis of EMs, and it is proven in a large number of experiments on EMs rat model in the presence of blood stasis. In the theory of Traditional Chinese Medicine "qi is mother of blood ", which means blood is the carrier of qi and qi exists in body attaching to blood. If the blood circulation tends to blood stasis, qi will move slowly, which becomes the syndrome of qi stagnation. Therefore, although there is not syndrome intervention on rat model, but the syndrome has been changed from blood stasis to qi stagnation and blood stasis due to the disease progressing. This can be some clues for further study of EMs syndrome development.Summing up the above conclusion, this paper uses the method of decomposition according to different effectiveness, and research the prevention and treatment on EMs mechanism by BSHPS and its decompositions in terms of Th1/Th2 drift, immune related cytokines and monoaminergic nerve and so on. The results show that BSHPS and its decompositions has effect of inhibition of Th1/Th2 cell drift of peripheral blood on EMs rats; BSHPS and its decompositions effect on EMs immune cytokines in the peripheral blood and endometrial changes, which reveals the mechanism of action of BSHPS and its decompositions on hypothalamic monoamines neurotransmitter. Above all, BSHPS is applied to treat EMs by inhibiting Thl/Th2 drift, decreasing immune related cytokine content, preventing ectopic endometrium planting invasion and angiogenesis mechanism. At the same time, it is used to regulate hypothalamic monoamine neurotransmitter secretion and activity so as to improve the state of liver-qi state. The three mainly effective components, operating qi, promoting blood circulation, warming meridian and blood tonic consisting, and its synergistic effect play an important role in treating EMs in every aspect. But the three effective components should work together to achieve the best result in all the links.In a word, the research about BSHPS uses the method of split demolition according to the different effectiveness, combined with modern medical theory. The research elaborates the effect and mechanism of BSHPS upon immune, "3A" mode and neuroendocrine cytokines network perspective in treating EMs. The research reveals part of target points of BSHPS in protein level. The research discusses the effect of operating qi, activating blood circulation, warming meridian and blood tonic according to the mechanism and target points of effections. This research lays the foundation for comprehensive understanding the mechanisms of BSHPS in treating EMs, knowing the target of all effections, streamlining and optimizating prescription.
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