| Irritable bowel syndrome (IBS), as a functional bowel disorder, is a symptom-based diagnosis characterized by chronic or repetitive abdominal pain and discomfort, alteration of stool consistency and a change of bowel habits. To date, its organic cause and pathogenesis is yet unknown. It is widely believed that IBS is caused by joint efforts of various interrelated factors, including gastrointestinal hypomotility, increased sensitivity of visceral organs, intestinal inflammation, the immune system’s malfunction, and psychosocial factors. IBS’s pathophysiological basis mainly lies in gastrointestinal hypomotility and abnormal sensitivity of visceral organs, the cause of which is not yet elaborated. In recent years, more focus has been on studying the interrelation between the nervous system, endocrine system and immune system to probe into the cause of IBS. IBS is not included in the name of diseases defined in the field of traditional Chinese medicine. Based on its clinical phenomena, IBS shall fall into the category of abdominal pain, loose bowels and melancholia, mainly caused by exogenous pathogenic factors, improper diet, emotional disorder and frail visceral organs etc. Basically, in modern medicine, treatments like dietary adjustments, medication and psychological interventions are often used to help relieve some symptoms of IBS. Yet there is a lack of drug therapy that proves to be safe and effective. Meta analysis of reports on IBS clinical treatment based on syndrome differentiation widely used by traditional Chinese medical workers in ancient times and nowadays highlights the strengths of traditional Chinese medicines in the management of IBS and its huge potential for a cure for IBS. In the light of this, the key is to probe into the pathogeny and mechanism of IBS and then to derive an effective treatment for better clinical results, with added clinical value and positive social outcomes.This dissertation is comprised of two main parts:literature review and laboratory test. To facilitate the study, IBS-D rat group modeling is established and Warming Kidney and Tonifying Spleen interventions are introduced to probe into its curative effects on IBS-D and to see how it functions, with the aim to explore a probable treatment of diarrhea-predominant irritable bowel syndrome with the use of traditional Chinese medicine. Part Ⅰ Literature Review1) The state of art of IBS animal model research is presented in aspects of IBS target group selection, IBS model duplicate, IBS syndrome model research shortcomings and prospects.2) The state of art of the study on the positive effects of proper modulation of nervous-endocrine-immune system on the management of IBS.Part Ⅱ Laboratory TestSection I:IBS-D Rat Group Modeling and Assessment on the Effects of Warming Kidney and Tonifying Spleen Interventions on IBS-DObjective:IBS-D rat group modeling is established to assess the effects of Wanning Kidney and Tonifying Spleen Interventions on IBS-D through observing the rats’general status, stool properties, AWR ranking and histopathological changes.Methodology:Referencing AL-Chaer modeling, make a duplicate IBS-D rat group. After that, HDG, MDG and LDG are used separately for target rat groups, while the control group is treated with Decocting-free Sishen pill. Then, their general status, stool properties, AWR ranking and histopathological changes are observed.Findings:1) Compared with the normal group, zero variance is observed in terms of their relative growth rate (p>0.05) but there are prominent changes in their stool properties characterized by increased quantity of stool grains (p<0.05), higher Bristol ranking (p <0.05), higher average ranking of loose stool (p<0.05), higher dry and wet ratio (p<0.05). Their AWR ranking is p<0.05(on the basis of1.5ml), also higher than the normal group.2) After receiving treatment, the general status of all the groups gets better. Among them, those treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions have the best curative effects. During the process, all the rats get some weight in a normal manner, with zero variance in their relative growth rate (p>0.05). After the treatment, the rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions and the control group both recover to different degrees, yet with the former better than the latter and the LDG group in aspects of the quantity of stool grains, Bristol ranking, average ranking of loose stool, dry and wet ratio as well as the AWR ranking. A general view of tissue specimen and pathological observation of all the groups highlight no pathological changes in visceral organs.Conclusion:1) Study on this batch of model rats proves that high sensitivity of visceral organs is an appropriate point of intervention to probe into IBS-D.2) Wanning Kidney and Tonifying Spleen interventions prove to be effective to reduce the quantity of stool grains, lower the Bristol ranking, the average ranking of loose stool as well as the dry and wet ratio, contributing to the reduction of sensitivity of the rats’visceral organs to some extent. Section II Study on the Mechanism of Warming Kidney and Tonifying Spleen Interventions’Effects on IBS-DTest I Warming Kidney and Tonifying Spleen interventions’effects on IBS-D rats’ colonic mucosa, ileocecal MC and T cell subsetsObjective:Observe the effects of Warming Kidney and Tonifying Spleen interventions on IBS-D rats’colonic mucosa, ileocecal MC and T cell subsets to probe into the underlying mechanism from the immunological perspective.Methodology:Referencing AL-Chaer modeling, make a duplicate IBS-D rat model. After that, HDG, MDG and LDG are used separately for target rat groups, while the control group is treated with Decocting-free Sishen pill. Then, observe the changes in their colonic mucosa, ileocecal MC and serum T cell subsets.Findings:1) After the treatment, both the rats treated with HDG, MDG and LDG Warming Kidney and Tonifying Spleen interventions and the control group have decreased quantity of colonic mucosa and ileocecal MC as well as lowered mean optical density. Rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions prove to recover much better than those treated with LDG Warming Kidney and Tonifying Spleen interventions and the control group (p<0.05).2) Comparative analysis of the quantity of colonic mucosa and ileocecal MC:quantity of ileocecal MC is a little bit higher than that of ileocecal mucosa, while the mean optical density has zero variance (p>0.05).3) After the treatment, the ratio of CD4+/CD8+in the serum of the rats treated with HDG, MDG and LDG Warming Kidney and Tonifying Spleen interventions and the control group becomes higher. Rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions prove to have better results than those treated with LDG Warming Kidney and Tonifying Spleen interventions and the control group (p<0.05).Conclusion:Warming Kidney and Tonifying Spleen interventions prove to be effective to reduce the quantity of colonic mucosa and ileocecal MC as well as the mean optical density of MC, which in turn stimulates some immune response to restrain MC phenotype activation and degranulation. Moreover, through the interventions, the ratio of CD4+/CD8+in the serum of the rats becomes higher, which further contributes to the modulation of T cell subsets for improved immunity.Test Ⅱ Warming Kidney and Tonifying Spleen Interventions’Effects on the colonic mucosa and ileocecal CCK and MOT of IBS-D RatsObjective:Observe the effects of Warming Kidney and Tonifying Spleen interventions on IBS-D rats’colonic mucosa, ileocecal CCK and MOT to probe into the underlying mechanism from the gastrointestinal hormone perspective. Methodology:Referencing AL-Chaer modeling, make a duplicate IBS-D rat model. After that, HDG, MDG and LDG are used separately for target rat groups, while the control group is treated with Decocting-free Sishen pill. Then, immunohistochemistry and Western-blot analysis is employed to observe the changes in their colonic mucosa, ileocecal CCK and MOT.Findings:After the treatment, the quantity of colonic mucosa, ileocecal CCK and MOT in the rats treated with HDG, MDG and LDG Warming Kidney and Tonifying Spleen interventions and the control group is reduced to varying degrees (p<0.05). Basically, rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions prove to have better results than those treated with LDG Warming Kidney and Tonifying Spleen interventions and the control group (p<0.05)Conclusion:Warming Kidney and Tonifying Spleen interventions prove to be effective to reduce the quantity of colonic mucosa and the amount of released ileocecal CCK and MOT, which in turn reduces the intestinal sensitivity and also accelerate the degradation of CCK and MOT present in their body. This helps relieve some symptoms of IBS-D.Test Ⅲ Warming Kidney and Tonifying Spleen interventions’effects on IBS-D rats’ colonic mucosa, ileocecal VIP and lumbar intumescence Substance PObjective:Observe the effects of Warming Kidney and Tonifying Spleen interventions on IBS-D rats’colonic mucosa, ileocecal VIP and lumbar intumescence Substance P subsets to probe into the underlying mechanism from the neuroendocrine perspective.Methodology:Referencing AL-Chaer modeling, make a duplicate IBS-D rat model. After that, HDG, MDG and LDG are used separately for target rat groups, while the control group is treated with Decocting-free Sishen pill. Then, observe the changes in their colonic mucosa, ileocecal VIP and lumbar intumescence Substance P subsets via immunohistochemical and Western-blot.Findings:1) After the treatment, both the rats treated with HDG, MDG and LDG Warming Kidney and Tonifying Spleen interventions and the control group have decreased quantity of colonic mucosa and ileocecal VIP as well as lowered mean optical density. Rats treated with HDG and MDG Wanning Kidney and Tonifying Spleen interventions prove to recover much better than CG (p<0.05).2) After the treatment, both the rats treated with HDG, MDG and the control group have decreased the protein expression of lumbar intumescence Substance P as well as lowered mean optical density. Rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions prove to recover much better than the control group (p<0.05).Conclusion:Warming Kidney and Tonifying Spleen interventions prove to be effective to reduce the quantity of colonic mucosa and ileocecal VIP via interferring with the function of gastrointestinal dynamic absorption and secretion;inhibiting the small intestine and colon mucosa secretion of water and electrolytes by reducing SP, which can adjust the VIP, SP secretion or make the intestinal sensitivity of VIP, SP to a certain extent.Test Ⅳ Warming Kidney and Tonifying Spleen interventions’ effects on IBS-D rats’cytokinesObjective:Observe the effects of Warming Kidney and Tonifying Spleen interventions on IBS-D rats’Th1and Th2cytokines subsets to probe into the underlying mechanism from the neuroendocrine perspective.Methodology:Referencing AL-Chaer modeling, make a duplicate IBS-D rat model. After that, HDG, MDG and LDG are used separately for target rat groups, while the control group is treated with Decocting-free Sishen pill. Then, observe the changes in their serum,colonic mucosa,ileocecal Th1and Th2cytokines subsets via Elisa and Western-blot.Findings:1) After the treatment, both the rats treated with HDG, MDG and LDG Warming Kidney and Tonifying Spleen interventions and the control group have decreased quantity of serum, colonic mucosa and ileocecal Th1cytokines and enhance Th2cytokines From different levels as well as lowered mean optical density. Rats treated with HDG and MDG Warming Kidney and Tonifying Spleen interventions prove to recover much better than CG and/or LDG (p<0.05).2) Both quantity of Th1cytokines and Th2cytokines in rats ileocecal are higher than colonic mucosa(p<0.05).Conclusion:Warming Kidney and Tonifying Spleen interventions prove to be effective to reduce the number of activation immune cells, reduce the expression of Th1cytokines, increase the expression of Th2cytokines, thereby regulating Th1/Th2anti-inflammatory and immune regulation. |
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