The Research On The Relationship Between Inflammatory Cytokines And Impaired Glucose Metabolism In Rat Collagen Induced Arthritis

Background and Objective:Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease,which can lead to multi-system involvement, such as the respiratory system,cardiovascular system, urinary system, nervous system and endocrine system diseases.Recent studies reported that patients with RA have a significantly higher incidence ofmetabolic syndrome, which positively correlate with the erythrocyte sedimentationrate, disease activity (DAS28score), tumor necrosis factor-α, interleukin-1andinterleukin-6, so we think that the higher incidence of metabolic syndrome in patientswith RA is association with inflammation. At the same time impaired plasma glucose,insulin resistance and lipid metabolism disorders are the different components ofmetabolic syndrome. Another studies found that islet beta cell function is impaired innon-diabetic and non-on corticoids RA patients by a mechanism that seem to be, atleast in part, independent of insulin resistance. Impaired glucose metabolism in RApatients may additional accelerate the progress of atherosclerosis and otherextra-articular symptom in RA patients. To a certain extent, it increased the economicburden and mortality rate in RA patients, therefore impaired glucose metabolism fromRA worthy of our attention. However, the mechanism of impaired glucosemetabolism from RA and leading to a significant increase in the incidence of diabeteshas not taken a clear report.To explore the possible mechanism of impaired glucose metabolism from RA.This experiment observed fasting glucose and insulin levels, expression of apoptosisprotein caspase-3in pancreatic beta cell, and analyzes the relationship of thesechanges and inflammatory cytokines, trying to expound the possible mechanism ofimpaired glucose metabolism from collagen induced arthritis (CIA).Method:1. Establish collagen induced arthritis rat: Experimental arthritis model wasestablished by Intradermal injection type Ⅱ collagen and complete Freud，s adjuvant,except the normal group (n=8).Use arthritis index, the successfully induced collagen induced arthritis (CIA) were classified as model group (n=6), through ankle HEstaining further confirmed the success of established models.2. Level of fasting glucose and insulin:17days after the first immunization，using glucose oxidase method measure fasting blood glucose levels, fasting insulinlevels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), thenanalyze the differences between two groups by SPSS20.0.3. Expression of apoptosis protein caspase-3in pancreatic beta cell:17days afterthe first immunization, apoptosis protein caspase-3in pancreatic beta cell weredetected by immunohistochemistry, then analyze the differences between two groupsby SPSS20.0.4. concentration of TNF-α and IL-6:17days after the first immunization, usingELISA measure blood serum TNF-α and IL-6, analyze the differences between twogroups and analysis the association between TNF-α, IL-6and fasting glucose, insulinby SPSS20.0.Result:12-14days after the first immunization successfully established CIA model. Inthe17days, for fasting glucose, it was higher in model group than in normal group(6.22±0.94) mmol/L vs.(5.01±0.73) mmol/L, P＜0.05. For fasting insulin, it waslower in model group than in normal group (9.38±0.4) ng/ml vs.(14.76±2.48) ng/ml,P＜0.05. For serum IL-6, it was higher in model group than in normal group(503.49±104.04) pg/ml vs.(343.02±75.73) pg/ml, P＜0.05. For serum TNF-α, it washigher in model group than in normal group (748.14±96.44) pg/ml vs.(222.44±25.17)pg/ml, P＜0.05. The expression of caspase-3in pancreas islet was higher in modelgroup than in normal group. Correlation analysis showed that TNF-α and IL-6levelsare significantly correlated with fasting plasma glucose and insulin concentrations(P<0.05).Conclusion:1. Fasting glucose in model group is significantly higher than in normal group,fasting insulin in model group is significantly lower than in normal group, indicatingthat there is a clear impaired glucose metabolism in CIA rats.2. Serum TNF-α and IL-6is significantly higher than in normal group, the change of HE staining in synovium of ankle joint is consistent with CIA and RA,indicating the presence of high levels of inflammatory cytokine in CIA rats.3. Fasting glucose levels was significantly correlated with the expression ofserum TNF-α and IL-6, fasting insulin levels was significantly correlated with theexpression of serum TNF-α and IL-6.4. The expression of caspase-3in pancreas islet was higher in model group thanin normal group. The expression of caspase-3as a terminal event of apoptosis,indicating the apoptosis of pancreas islet in CIA rats was significantly higher than innormal rats.5. The elevated fasting glucose in CIA may be associated with the reducedfasting insulin level which due to the over expression of caspase-3in pancreas islet.