Study On The Effects Of Long-term Alcohol Intake On The Expression Of TSLP In The Rat Gastric Mucosa Epithelium

Background:A high alcohol intake is significantly associated with diseases of the gastrointestinal tract, but less is known about the effects of modedrate consumption.The animal model of high alcohol intake is easily set up,however the moderate alcohol consumption is less known.Taylor B drawes the conclution in the method of a systematic computer-assisted literature review that moderate alcohol consumption may play a positive or negative role in disease etiology, but overall conclusion is that moderate alcohol intake in not a high risk factor for many of the gastrointestinal diseases associated with high levels of consumption.Alcohol drinking is responsible for a number of gastrointestinal disease. Although heavy drinking episodes and chronic drinking are well linked to mechanisms of disease, mmoderate alcohol consumption and its effects are less well known. Epidemicological studies show moderate alcohol intake is a risk of liver disease, tumor of esophagus, and pancreasis, but it is positive to chronic gastritis and cholecystolithiasis. About95%alcohol in body in break down in the way of oxidation, including oxidation via first-pass metabolism(FPM), oxidation via microsomal ethanol-oxidizing system(MEOS), and fatty acid-catalase, aldehyde dehydrogenase system。 FPM occurs when a certain amount of ingested ethanol is metabolized primarily in the stomach and in the liver before reaching the systemic circulation. Lieber et al. have investigated this phenomenon extensively. They have emphasized that FPM is predominantly of gastric origin and that gastric ADH is mainly responsible for the FPM. Ethanol oxidation by alcohol dehydrogenase, aldehyde dehydrogenase is the main system used, with the other two only joining in during chronic ethanol ingestion. ADH meidate in alochol oxidation in a manner of transfering hydrogen in ethanol to NAD, producing aldehyde and NADH respectively. Aldehyede make use of NAD to produce acetic acid, and the latter is transformed into Acetyl coenzyme A which join in Crebs cycle generating water and carbon dioxide.As the consumption of alcohol increase and store up, MEOS works to generate OFR and ROS resulting lipid peroxidation of cell membrane system including mitochondria. The cell in the station of oxidative stress. The expression of transcription factor HIF1-α enhances to accommodate hypoxia.In the year of1992, HIF1was first detected by Semenza, Wang. The HIF1complexes are the mayor transcription factors that are reponse to low oxygen conditions. It is heterodimers that are composed of the constitutively expressed HIF1β subunit and HIF1a subunits, which are rapidly stablilized on exposure to hypoxia. Once activated HIF1amplifies the transcription of genes encoding glucose transporters and most glycolytic enzymes, increasing the capacity of the cell to carry out gycolysis. In addition, HIF1activates the pyruvate dehydrogenase kinases, which inactivate the mitochondrial pyruvate dehydrogenase complex and thereby reduce the flow of glucose-derived pyruvate into the tricarboxylic acid (TCA)cycle. This reduction in pyruvate flux into the TCA cycle decreases the rate of oxidative phosphorylation and oxygen consumption, renforcing the glycolytic phenotype and sparing oxgen under hypoxic condtions.HIF1-α playes role in immunoregulation.TSLP derived from epitheial cells can trigger DCs directly in mucosa and promote the latter secret OX40L to polarize to the TH2immune from THO immnue.In the normal station, DCs are present in the mucosa. TSLP is a anti-inflammatory cytokine.Whether TSLP can be inducible in the gastric mucosa is unkown.Objectives:To study the role of alcohol metabolism in the pathogenesis of ethanol-induced gastric mucosa injury Methods:Wistar rats were used in the study. A gastric mucosal injury model was established by alcohol gavage to rats. Gross and microscopic apperarance of gastric mucosa wer evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Guth and Mascuda criterion were adopted to evulate the gastric epithelium injuries respectively.Results:For the groups of15%, MDA, LI and the pathological injury changes insignificantly (p>0.05). The gastric mucosal lesion index was correated with the MDA content in gastric mucosa. As the concentration of alcohol was elevated and exposure time to alcohol was extended, the context of MDA in gastric mucosa increased and the extent of damage aggravated as far as groups of30%and45%. The lesion index and the pathological injury increased in groups of30%and declined in group of45%as the exposure time extended(p<0.01).Conclusions:In the level of5ml/kg/d15%v/v, the rat gastric mucosa oxidative stress is not apprant.Long-term alcohol consumption causes lipid peroxidation in the gastric epithelial cells. The cells are in the station of oxidative stress as the concentration of alcohol was elevated and exposure time extend.. Background:Long-term alcohol intake leads to lipid peroxidation and ROS through FPM, MEOS, catalase which depletes inherent reducing agent NADPH in rat gastric mucosa. The function of transcrpiton factor HIF-lastrengthenes to adapt to the station of hypoxia. HIF-1αwas found in the year of1992,of which the target genes includes more than200kinds involving in energy metabolism, angiogenesis, nitric oxide synthesis, iron and heme metabolism and immunoregulation. Thymic stromal lymphopoietin derived from epithilial cells act on myeloid dendritic cells and lymphoid dendritic cells to regulate adaptive immnune which plays crucial roles in the initiation and promotion TH2immune.TSLP binds to TSLPR directly promoting TH2polarization from THO via CD40L.The resultant humoral immunity involves in eradication of extracelluar bacteria and parasite.The pathway activating DCs is independent of the way of the classical MHCII, costimulatory molecules.Up to now, it is not reported whether TSLP is expressed in gastric mucosa and what the mechanism lies. We assume that long-term alcohol intake activates HIF-1α leading to expressing of target TSLP. The assumption will rich the mucosa immnne theories, and explain why moderate alcohol intake helps to eradicate HP partly.Objectives:to study the expression of tslp,hif-la in the state of oxidative stress in gastric mucosa caused by long-term alcohol intake, and to analyse the expression correlation between them.Methods:Immunohistochemistry was applied to locate TSLP, and HIF-la. RT-PCR and Western blot were used to measure the amont of TSLP, HIF-la in cytoplasm in the level of mRNA and protein respectively.Results: TSLP, HIF-la in different groups were all detected by means of immunohistochemistry compared to control group. TSLP, HIF-la were located in gland cells and the location were consistent. In group15%and30%the mount of TSLP, HIF-la increased as exposed time extended while In45%group, the mout of TSLP, HIF-1αa declined. The expression of TSLP was related to expression of HIF-1α.Conclusions:Protein HIF1-α, TSLP are not induced in normal rat gastric mucosa. As the level of oxidative stress get intense,protein HIF1-α and TSLP express increase.Alcohol can trigger TSLP expression via HIF-la in rat gastric mucosa...