| Background and aimsUlcerative colitis (ulcerative colitis, UC) is a chronic non-specific colitis, lesions were accumulated in mucosa and submucosa of colon, lesions often start with remote colon. UC and Crohn's disease (Crohn's disease, CD) are area of inflammatory bowel disease (inflammatory bowel disease, IBD)Europe and North America over the past presented higher incidence of IBD population, the Asian population incidence is relatively low, but in recent years in the Asian population in IBD showed significantly higher incidence trends. IBD pathogenesis is still not very clear, current studies suggest that may be related to genetic susceptibility and populations in intestinal infections, and intestinal mucosa barrier defect under the effect of environmental factors such as changes caused by abnormal intestinal immune system response.The domestic formation studies demonstrated that smoking, the appendix excision, the enteral infection affect the occurrence of IBD; Drinks the tea, breast feeding is the protection factor of UC; highly educated and urban populations are more IBD; Vice Mycobacterium tuberculosis infection may be related with the CD. Recent studies show that intestinal barrier dysfunction was exceptionally close with the IBD morbidity. The enteric cavity surface area is very big, becomes by the epithelial cell zonula occludens, exposes for a long time in each kind of dietary ingredient the paragenesis fungus and the disease germ. The intestinal tract epidermis has the important barrier function, In the most situations, the epithelial cell to each kind of damage stable reply, the inflammation is at the limit condition. When IBD occurs, the intestines mucous membrane barrier dysfunction, the mucous membrane permeability advances, causes in the enteric cavity to activate the immune cell material shifting and so on bacterium,antigen to the mucous membrane inherent level, the induction mucous membrane excessive immune response occurrence, subsequently further destroys the intestines mucous membrane barrier, the aggravation mucous membrane unusual immune response, thus causes the occurrence of IBD.UC and CD under normal circumstances can be the basis of clinical manifestations, laboratory and radiological, endoscopic and histological features of a comprehensive analysis is not difficult to identify. Distinguishes UC and CD with difficulty for a while regarding the colon inflammation enteropathy, clinical may diagnose is the IBD type undetermined (type unclassified, IBDU), observe the patient's condition. However, if extensive colon lesions, and endoscopic and pathologic findings are not typical, sometimes UC and CD with difficulty distinguish; If the IBD endoscopic inflammation is light, without typical endoscopic changes, but also need to be differentiated from intestinal infectious diseases. CD,intestinal tuberculosis.intestinal lymphoma.intestinal Behcet's disease because there are many similar endoscopic places, these diseases Between the clinical identification is a problemCurrently, the clinical laboratory yet simple approach to the differential diagnosis of IBD:blood, plasma proteins, electrolytes, ESR, C-reactive protein, the unit can also do conditional fecal calprotectin, lactoferrin, al antitrypsin and other tests, but these tests are nonspecific. Imaging studies, including gastrointestinal barium, abdominal ultrasound, CT, MRI and other help for the diagnosis of IBD.Our group use proteomics technology to screen out the differences between UC and normal intestinal mucosa of several proteins, including 3-hydroxy -3--methylglutaryl coenzyme A synthase 2.PPARy is a research hotspot in recent years, is a nuclear transcription factor, that is a member of peroxisome proliferator-activated receptor, according to the different structure, PPAR can be divided intoα,β(orδ) and y are three types, the genes were located on human chromosome 22,6 and 3. Usually rich in mitochondria with high expression of PPARa andβ-oxidation activity of the organization, such as liver, intestinal mucosa, kidney cortex and heart, while in some other organizations also found a low level of expression of PPARa; PPARy is in adipose tissue, bladder and bowel in High expression; and PPARβin almost all organizations have a low level of expression. PPARy through the adjustment related gene's expression, playing an important role in the formation of fat, glucose and lipid metabolism, the immune system, and involvement of occurrence and development with a variety of diseases such as diabetes, obesity, hypertension, cerebral ischemia, Parkinson's disease, kidney disease, cancer. PPARy at home and abroad on animal studies with IBD have some reports, most studies support the protective factor PPARy is the IBD, but also hold the opposite view that the pre-treated with PPARy agonists in animal models will Increase the animal's intestinal inflammation caused more ulcers, glandular loss, and edema. Although many animal experiments in vitro with IBD reported on PPARy, but currently only a small amount of experimental evaluation of the PPARy receptor in patients with UC and CD expression and function. HMGCS2,the 3-hydroxy-3-methylglutaryl coenzyme A synthase 2, the formation of ketone bodies regulating the key enzyme in the liver and some extrahepatic tissues such as skeletal muscle, heart, pancreas, testes, colon in both Expression, HMGCS2 expressed in the role of these organizations need to be further elucidated. However, in the organization, HMGCS2 can be oxidized fatty acids, HMGCS2 expression can prevent the deposition of acetyl coenzyme A, which in turn can be reduced fatty acid oxidation rate. Colon's ketogenesis and HMGCS2 express related, the latter depends on the gut-generated acid salt, in healthy intestinal epithelial cells, butyrate stimulation of cell proliferation, however, in the organization of the tumor cell lines it Reduce proliferation and induce cell differentiation and apoptosis. The overseas some scholars proposed that uses in explaining" the butyrate is contradictory", this hypothesis thought:The healthy intestines mucous membrane decomposes the butyrate effectively, thus causes in the cell the butyric acid salinity drop. thus prevents ability drop which multiplies, decomposes the butyrate in the colon cancer cell line anergia, under this situation some scholars proposed that the HMGCS2 induction caused the fatty acid beta oxidation to be weaken deficient. Colon butyrate is the main fuel source, and there is evidence that oxidative damage in ulcerative colitis, in active and quiescent UC CO2 in the oxidation of butyrate and ketone bodies was significantly lower than in healthy controls Group, and this decrease is related with the disease. The butyrate oxidized flaw had reflected the UC patients' invariable and clear metabolism flaw. reducing the oxidation of butyrate can be explained by the distribution in the colonic inflammation, in particular, the incidence of frequency end of the colon. Generally believed that the fatty acids (n-butyrate) oxidation defect is the lack of a colon energy performance. Because the lack of HMGCS2 induction, the beta oxidation of the fatty acid (the n- butyrate) is weaken. UC patients have defects in butyrate oxidation, due to butyrate oxidation of ketone bodies and CO2, we assume, as a key enzyme in ketone bodies generated in HMGCS2 mucosa of UC patients also reduced. HMGCS2 in UC, CD patients and its role in the expression of the intestinal mucosa so far no studies have reported.Therefore, the purpose of this experiment is to by UC, CD and normal healthy control group were HMGCS2, PPARy system detects molecular markers to observe the relatively complete HMGCS2, PPARy in both the expression of disease, which suggested:(a) whether they can be as a maker to distinguish UC from CD (b) whether they are associated with Energy metabolization obstacle and dysbacteriosis; (c) through the UC, CD and healthy control group, the development of IBD analyzed the molecular basis.Materials and Methods1. A total of 204 colorectal specimens were collected randomly from individuals who underwent endoscopic resection under total colonoscopy. The specimens consisted of 73 case of UCs,42 CDs and 89 healthy controls.compared between the UC group and CD group general information on clinical features and check the differences, including sex, age, lesions involving the location, Activities staging, clinical indexing, Endoscopic features, time of onset etc.2.1mmunohistochemical staining observed HMGCS2, PPARy in the expression of each group3. Statistical analysis:SPSS 13.0 statistical software for analysis, with the Independent-Samples T Test Determination of the age group and differences between-groups of patients; R* C table using theχ2 test to compare group data between the positive expression rate; Using non-parametric test of two independent samples,K independent samples of non-parametric test and Mann-Whitney U test comparing the groups of gender, age, lesion site, stage, degree of clinical, endoscopic grading related with protein dyeing and expression differences All results obtained bilateral P value, P<0.05 considered significant difference.Results1.73 UC patients consisted of 46 males and 27 females, male:female= 1.70:1, age 13-77 years, mean age (40.07±14.39) years, peak age of onset is 30-49 years, of which 28 cases occurred in the rectum (38.4%),9 cases occurred in the rectum, sigmoid colon (12.3%), The whole colon in 25 patients (34.2%).42 cases of CD patients,29 cases occurred in the terminal ileum and small intestine (69.0%).2. HMGCS2, PPARy in 73 patients with positive expression in intestinal mucosa of UC patients were 48 cases (65.8%) and 36 patients (49.3%); in 42 patients with positive expression in intestinal mucosa of CD patients were 37 cases (88.1%) and 30 patients (71.4%); in 89 cases of normal mucosa positive control group accounted for 82 cases (92.1%) and 66 patients (74.2%). HMGCS2, PPARy in the colonic mucosa in UC patients and normal healthy controls and CD patients significantly decreased compared intestinal mucosa, the difference was statistically significant (P<0.01), but in CD patients and healthy controls intestinal mucosa HMGCS2, PPARy expression was not Significant difference, not statistically significant (P-0.521 and P=0.742).3. HMGCS2, PPARy in intestinal mucosa of patients with active UC was significantly less than the expression of intestinal mucosa in remission, the difference was statistically significant。(HMGCS2:P=0.002. PPARy:P=0.008)4. HMGCS2, PPARy expression in the intestinal mucosa of UC patients with gender, age, disease location, clinical, no significant correlation was found. The expression of PPARy protein in patients with endoscopic grade UC was no significant correlation, but HMGCS2 protein expression and endoscopic grading, endoscopy is low grade inflammation in mild disease is relatively high when the protein.ConclusionsThe study found HMGCS2, PPARy is not IBD specific protein targets, but also in healthy controls and other mucosa, for the identification of UC, CD has a certain significance, may be used as an indicator of the severity of UC. HMGCS is a key enzyme in ketone body formation, PPARy addition to factors involved in inflammation and inflammation-related regulation of transcription factors, there may be similar with the HMGCS by butyrate and intestinal energy metabolism and the role of intestinal flora in IBD The occurrence and development... |
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