Study Of Protection And Mechanism Of Taurine On Acute Hypoxia Induced Rat Intestine Damage

In high altitude area over 3 000 meters,hypobaric hypoxia can lead to obvious indisposition of stomach intestine such as nausea,vomit,decreased appetite,abdominal distention,vague pain et ct.Some studies report that acutely advancing to plateau over 4 000m,occurrence of hemorrhage of peptic ulcer would be 63.1%,hemorrhea would be 55%, recurrence of ulcer would be 67%and perforation would be 25.6%.It is thus evident that high altitude hypoxia can cause serious injury to gastrointestinal digestion;however,there is a deficiency in studies how to protect intestinal mucosa and intestines tissue from hypobaric hypoxia damage.Taurine,one of sulfur amino acids and conditional essential amino acids,wide exists in various tissue of body especially in excitable tissues of muscle,nervous system, glandular organ.Studies suggest taurine is multifunctional agent of protecting cardiovascular system,modulating nervous system,promoting digestion and detoxication. Furthermore,taurine possesses cytoprotection activities and is notable to act as an antioxidant,membrane and Ca²⁺ stabilizing agent.Researches indicated taurine could significantly prevent brain and retina injury from hypobaric hypoxia through decreasing platelet aggregation,inhibiting neurotoxicity of excitatory amino acids,modulating stabilization of Ca²⁺,reducing synthesis of NO and free radical,resisting lipid peroxidation, inhibiting apoptosis and enhancing expression of hypoxia inducible factor.However, whether taurine could protect intestinal mucous membrane and intestinal tissue from hypobaric hypoxia damage is not clear,there is a lack in this field.Intestinal mucous epithelial tissue is the place to absorb nourishments for the body and it is also an important barrier for resisting invasion of bacteria.Therefore,it plays a role in energy metabolism and various physiologic functions.The metabolism of intestinal mucous epithelial tissue is high,oxygen concentration in blood and organization is essential to maintain various physiological processes of intestinal mucous cells.Hypobaric hypoxia could lead to serious damage to intestinal mucous epithelial tissue;therefore it is necessary to search effective way to relieve intestine injury caused by hypobaric hypoxia for precaution from high altitude reaction.Hypoxia-inducible factor is a kind of transcription factor which wild exists in mammals and human being and expresses in anoxia condition. Hypoxia-inducible factor is the necessary nuclear signal for the organism response of adaptation reaction to hypobaric hypoxia;it plays a key role in these processes. Hypoxia-inducible factor-1(HIF-1),consisted of two protein subunits HIF-1αand HIF-1β,would bring out when cells in ischemic or hypoxia conditions and exert critical effect on adaptation reaction;it can promote a serial of adaptive responses to oxygen deficiency by means of regulating the transcription and expression of down stream target genes.This is the conclusive and common molecular mechanism of hypoxia-induced genes transcription and hypoxia signal conduction.Considering to the critical role in the adaptive response to hypoxia,HIF-1 is called housekeeper transcription factor of hypoxia regulation.Acute high altitude hypoxia can cause serious absorb and metabolism dysfunction of glucose,even lead to energy exhaustion.The blood sugar level of body is extremely sensitive to the hypobaric hypoxia.Hypobaric hypoxia can significantly decrease the blood sugar level,impact the normal energy metabolism and function of the body.Glucose transports(GLUTs) are important proteins in charge of absorbing and transporting glucose in the body.GLUT2 and GLUT5 are vehicles in the intestine tissue to absorb and transport glucose.Therefore,the expression and modulation of GLUT2 and GLUT5 play an essential role in the process of glucose absorb and metabolism in the body.Based on the analysis above,we presume taurine maybe an effective protective agent of intestine tissue damage induced by hypoxia.Taurine could significantly protect intestinal mucous membrane, promote the absorption and transport of glucose,the mechanism of the effect involves increasing expression of HIF-1 and GLUTs,enhancing the body adaptive response to hypoxia.The purpose of this study was to determine whether taurine could protect intestine tissue from hypoxia induced rat intestine tissue damage and the associated molecular mechanism.A rat model was used to simulate 4 500 meters or 5 500 meters high altitude hypoxia conditions in low-pressure chamber and observations were taken in many phase points.Immunohistochemistry,transmission electron microscope,RT-PCR and western blotting method were used to study the structural and functional damage of the intestine tissue induced by acute continuous hypoxia,also as the proective effects of taurine and the associated molecular mechanism concerned with HIF-1 and GLUTs.The main results and conclusions were summarized as follows:1.The observation results of immunohistochemistry and transmission electron microscope to the morphous,structure and ultrastructure of intestine mucous epithelial cells suggested acute hypobaric hypoxia could induce serious structural and functional damage to the intestine mucous epithelial cells,symptoms including cellularedema,hemorrhage, disorder and defluxion of intestinal villus.Ultramicrostructural observation showed a series of cellular damages including intumesces of the chondriosome,distension of endocytoplasmic reticulum,disorder of the cellular structure.Taurine nutritional treatment could significantly relieve the intestine mucous epithelial cells damage induced by hypobaric hypoxia according to the state of intestinal villus,cellularedema,hemorrhage and the structure of the microvillus,chondriosome,endocytoplasmic reticulum and other inner cellular conditions.2.Results of RT-PCR and western blotting showed in the hypobaric hypoxia condition the expression of HIF-1αand HIF-1βin intestine tissue of rats significantly increased and reached the peak after 12h,then gradually decreased.Taurine nutritional treatment could significantly promote the expression of HIF-1αand HIF-1βin intestine tissue of rats in hypobaric hypoxia condition.3.In the hypobaric hypoxia condition,the serum glucose level and the expression of GLUT2 and GLUT5 in intestine tissue of rats significantly decreased.Taurine nutritional treatment could effectively inhibit the decrease of the serum glucose level and the expression of GLUT2 and GLUT5 induced by hypobaric hypoxia.Above all,the study suggested taurine nutritional treatment could effectively relieve the intestine tissue damage induced by acute hypobaric hypoxia and significantly extenuate the intestinal mucous epithelial cells injury,and inhibit the decrease of the serum glucose level.The mechanism of effects maybe associated with the fact that taurine could promote the expression of HIF-1α,HIF-1β,GLUT2 and GLUT5 in intestine tissue of rats in the hypobaric hypoxia condition,enhance the ability of adaptive response to hypoxia and glucose absorption and transport.