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The Mechanism Study of Barrier Injury and Intervene on Intestinal Mucosa during Rats Exposed to High Altitude

Author: WuWenMing
Tutor: ZhangFangXin；KangShengChao
School: Fourth Military Medical University
Course: Internal Medicine
Keywords: Plateau Hypoxia Intestinal mucosal barrier Hypoxia-inducible factor -1α Inducible nitric oxide synthase
CLC: R594.3
Type: Master's thesis
Year: 2010
Downloads: 30
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Abstract

Background plateau hypoxia, cold, high wind speed, high evaporation, high radiation, climate variability, climate, geographical features, when the human body into this area, the air pressure difference caused by the altitude, the oxygen content of less dry air and other changes can cause the body to low oxygen partial pressure of oxygen decreased alveolar oxygen partial pressure and thus fall transported to a decrease in the amount of oxygen in the blood. Therefore caused by the reaction of the body: the respiratory rate increase, the more air is inhaled into the lungs; increase in heart rate and cardiac output to increase arterial blood flow through the lungs and body; the body gradually increase the formation of red blood cells and hemoglobin, improve the ability of the blood to transport oxygen. But even if the above adjustments, nor can people who recently reached the plateau of the play should be a normal physiological performance impact of multi-system of the body, is apt to cause systemic respiratory, nervous, digestive and other multi-system reaction. At home and abroad on altitude sickness patients with respiratory, circulatory and nervous dysfunction more, but less on the digestive system, especially intestinal mucosal barrier injury research. With in-depth research of the intestinal complex physiological function, noted that the gut is not only important organs of digestion and absorption of nutrients, and the intestinal tract also has immunomodulatory, endocrine function, mucosal barrier function. Intestinal barrier function (gut barrier function) has become a research focus. The intestinal mucosa screen damage can often lead to intestinal mucosal barrier dysfunction, intestinal mucosal barrier dysfunction can further aggravate the condition of the primary disease, and even induced multiple organ dysfunction, systemic inflammatory response syndrome, creating a vicious cycle, life-threatening. It is in the natural environment caused by high altitude hypoxia model basic experimental research, study its pathogenesis and interventions, it is particularly urgent, but also laid the foundation for subsequent clinical trials. Purposes through the establishment of a rat model of the natural environment of the different altitude and time point to high altitude, to dynamically observe pathological changes of the intestinal mucosa, and immunohistochemistry was used to detect the expression of hypoxia-related factors. Clear mucosal protective agent the Gln agent whether hypoxia-induced intestinal mucosal injury prevention plateau, to further explore the relationship between hypoxia associated factor with high altitude hypoxia pathogenesis. The method in this study to be through the establishment of the natural environment of the different altitude and time point plateau rat model of hypoxia and dynamic optical microscopy and electron microscopy to observe the change in the morphology of the intestinal mucosa, and quantitative assessment, using immunohistochemistry method of detection of intestinal mucosal hypoxia-inducible factor-1α (hypoxia inducible factor-1α, HIF-1α) and inducible nitric oxide synthase (Induced Nitric oxide synthase; iNOS) expression from both altitude and time point to explore the high altitude that there is no damage to the intestinal mucosa and two-factor in the damage mechanism. Intervention use the intestinal mucosa protective agent glutamine (Glutamine, Gln), and as a control group in the saline group, observed the microscopic histological parameters change and hypoxia-related factors change, further judge glutamine at high altitude damage intestinal tissue outcome affect its ability to reduce the expression of iNOS to play a protective effect on the mucous membrane under hypoxic conditions. Results (1) successfully established different altitudes in the natural environment and the time point in rat intestinal hypoxia model, HE: Plateau group of intestinal villi from swelling, shortening and thickening to lodging, fusion, damaged or even broken exfoliation, inherent layer exposed, interstitial congestion inflammatory myeloid exist. The extent of the damage with increasing altitude and exposure time increased. The scanning electron microscopy showed that: the top of the plateau rats damage light intestinal villi small amount of exfoliation and inflammatory substances oozing local damage, ulceration, severe visible surface of the intestinal villi full of holes in the honeycomb structure; holes of different sizes, diameter of 10 ~ 20μm; entire structure of the mucosa of the small intestine has been completely destroyed, there is only a \Preliminary evidence of intestinal mucosal injury in hypoxic conditions aggravated with the increase in altitude hypoxia time. (2) explicitly hypoxia associated factor hypoxia-inducible factor-1α and inducible nitric oxide synthase expression in the 3842 group plateau (altitude 3842m, Yuzhong, Maxian Hill), plateau 4767m (altitude 4767m Hoh Xil, budongquan of) in intestinal mucosa above two factors express the amount of content with the plain group (altitude 500m, Shaanxi, Xi'an) the dynamic comparative showed a clear upward trend, the point in time the same altitude, 24h, 48h, 72h both compared with the plain group is also increasing. The prompt high altitude early can produce tissue damage of the intestinal mucosa. HIF-1α expression can be induced intestinal mucosal enhanced with the expression of iNOS protein increase, and both increase is always a positive correlation, suggesting that HIF-1α may be involved in iNOS protein expression and intestinal mucosal injury of intestinal tissue. (3) mucosal protective agent glutamine the plateau hypoxia-induced intestinal mucosal injury protection. The plateau drug intervention group 24h, 48h, 72h histological morphology are good at the same time point the control group, hypoxic injury factor iNOS expression and intestinal mucosa lower than the control group, suggesting that glutamine is possible by reducing the expression of iNOS gene to play the role of intestinal mucosal protection. The conclusion of this topic through the successful establishment of the natural environment in the intestinal mucosa of rats plateau hypoxic injury model confirmed the high altitude hypoxic damage of the intestinal mucosa, showed that of HIF-1αe and iNOS in hypoxic injury pathogenesis played an important role; mucosal protective agent can effectively inhibit hypoxic injury associated with downregulation of iNOS gene expression. The results of in-depth exploration of the plateau hypoxia gastrointestinal possible pathogenesis and new therapeutic direction to provide a preliminary experimental data and theoretical basis.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Physical damage > Altitude sickness,altitude sickness,oxygen deficiency
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