| Diarrhea is not only an independent disease, but also a symptom in the pathological process of various diseases. Statistics show that every year 836 million people suffering from diarrhea, therefore, The Ministry of Health focus it as one of important diseases. Modern medical research suggests that many pathogens can cause diarrhea, it has complicated mechanisms. Its occurrence is based on the disorder function of gastrointestinal tract, such as secretion,digestion, absorption dysfunction, it can induce increased secretion, less food absorption and biodegradable and less digestion. Inflammatory mediators is major autologous active substances causing diarrhea. Clinical practices found that the majority of diarrhea diseases (including infectious and non-infectious) most of the pathogens can induce intestinal inflammatory, release all sorts of inflammatory mediators. Therefore, the anti-inflammatory drugs can treat diarrheal by inhibiting inflammation and the synthesis of inflammatory mediators release.Papaver nudicaule L. is a perennial herb. It has been used for treating diarrhea among the northern minority for a long time. In previous studies it was found that Papaver nudicaule capsule and the whole plant extraction has a strong effect on treating diarrhea, it can quickly ease or even eliminate diarrhea and relieve abdominal pain symptoms. Comparing with the similar drugs it has obvious advantages in anti-diarrhea without changing the gastrointestinal microflora and the environment. So from the point of modern science and in-depth study, it reveals material base of national medicine, mechanism, will have a major impact on national medicine research and development, production and clinical use. This thesis mainly focus on mechanism of the Papaver nudicaule L. water decoction for anti-diarrhea; the intestinal epithelial cells and the protective effect of anti-inflammatory analgesic effect study.The thesis includes two parts: literature reviews and experimental study. Literature reviews discuss the function of intestinal epithelial cells and inflammatory cytokines / cytokines in the process of diarrhea; general review of Chinese medicine treating acute and chronic diarrhea. Experiment research observes the behavior change of mice, intestinal morphology, pathological changes of serum interleukin-1 (IL-1β) and TNF-αlevel, expression of intercellular adhesion molecule-1 (ICAM-1) and the proliferating cell nuclear antigen (PCNA) as well as their effect on epithelial cells using senna gavage induced mouse diarrhea model. The experimental results are as follows: 1. Influencne of Papaver nudicaule water decoction on the changing of mice behavior small intestinal tissue lesions in the process of diarrheaIn the fourth day mice after administration senna gavage appear different extent of apparent diarrhea, performance times increased, dilute quality, in the seventh day,the model mice appear noticeably thinner state, and filthy fur,tiredness, anorexia and other symptoms. And diarrhea symptoms of mice in each administration group markedly improved, it showed a decreased performance time, quality changes such as from the quality of water to thin paste. good mental state, a normal diet, emotional seemed excited ,little weight gain. Normal intestinal epithelial cell is integrity with clear organizational structure and neat mucosa. Villus epithelial cell has rich cytoplasm, the nucleus is located at the base, elliptical in shape and clear, adjacent cells sound closely linked. There is relatively small number of goblet cells, scattered distribution. Within the lamina floor, there is no lymphocytes and other inflammatory cell infiltration.In the model group intestinal appearance have different levels of mucosal congestion and edema, thickening of bowel larger phenomenon. Microscopically, small intestinal swell, villi lost, normal intestinal structure lost, epithelial cells edema, connection cell structure defects. Goblet cells markedly increased with a large number of lymphocytes.Intestinal hyperemia and edema was improved in the control group. small intestinal is mild swelling and the villi has basically not lost, clear structure and little or no lymphocytic infiltration.2. Mechanism of Papaver nudicaule water decoction of inflammatory response intervention in the process of diarrheaGastrointestinal tract is not only the digestive system, but an important immunological organ. When function of immune system is abnormal, such as the transition immune responses or immune tolerance will lead to various gastrointestinal diseases, it can cause immune dysfunction. IL-1βand TNF-a are basic network cytokines of immune regulation, it can participate in a variety of body cell growth, differentiation and functional regulation it can play an important role in the process of immune and inflammatory response. As inflammatory cytokine levels rise, it can further activate inflammatory process causing intestinal damage, and emerge mucolized congestive edema, or even erosion, bleeding. Because both IL-1βand TNF-αhas a strong inflammatory activity, they can directly have an effect on the vascular endothelial cells, which can increase its permeability, resulting in substantial leakage, Therefore, high levels of IL-1βand TNF-a can reflect permeability increasing of the gastrointestinal wall to some extent, they can lead to a series of diarrhea symptoms.The experiment is designed on the basis of the inflammatory response characteristics for diarrhea, using enzyme linked immunosorbent assay (ELISA) and immunohistochemical methods through quantitative and qualitative analysis of IL-1βand TNF-αlevel in the serum and tissue to illustrate the inflammatory response intervention function of Papaver nudicaule L. water decoction.Experimental results show that IL-1βserum levels of the model group is significantly higher compared with the normal group; TNF-αpositive expression of intestinal tissues have increased significantly. IL-1βlevel of each dose of Papaver nudicaule decreased significantly than the model group; Meanwhile; the expression of TNF-αis obviously decreased compared with the model group. It means that Papaver nudicaule can inhibit IL-1βand TNF-αexpression, reduce the inflammatory response, improve diarrhea symptoms and reduce diarrhea abdominal pain. It may be one of effective mechanism of treating diarrhea of Papaver nudicaule.3. Protection function of Papaver nudicaule decoction to the insestinal epithelial cellLeukocyte excessive activation is a key pathological process of the diarrhea, ICAM-1 as an immune modulator factor, via mediated different interleukin subsets of contact and adhesion via ligand interactions , regulate the function of leukocyte activity and immune response. Severe diarrhea can cause intestinal damage, increased intestinal permeability, intestinal barrier dysfunction. Recent studies have found that proliferating cell nuclear antigen (proliferating cell nuclear antigen, PCNA) reflects the intestinal epithelial cell proliferation status. The experiment investigated the influence of Papaver nudicaule decoction on expression of small intestine tissue of ICAM-1 and PCNA of diarrhea mouse using immuno-histochemical methods. The results showed that ICAM-1 expression in the model group was significantly higher than the normal group. Each dose of Papaver nudicaule group and the model group reduced expression, especially in the large and middle-dose group. PCNA expression of model group is obviously higher than normal group. Compared with each dose of Papaver nudicaule group and the model group, it also have different degrees of expression.Comprehensive analysis of each role of the above areas can draw conclusions: Papaver nudicaule decoction can significantly inhibit inflammatory cytokines IL-1β, inflammatory mediators such as TNF-αactivity in the process of diarrhea, It can played a role in anti-inflammatory. On the other hand, it can inhibit excessive activation of leukocytes by reducing the expression of ICAM-1 to protect intestinal mucosa; and through the promotion of epithelial cell proliferation, It can increase cell proliferation and self-healing capabilities and protect on intestinal epithelial cells in vitro. |
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