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Relationship Of Interleukin-25 Level With The Severity Of Hepatic Steatosis And M2 Macrophage Activation In Patients With Non-alcoholic Fatty Liver Disease

Posted on:2020-07-28Degree:MasterType:Thesis
Country:ChinaCandidate:H Y XiaoFull Text:PDF
GTID:2404330575493335Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Purpose:To explore the correlation between IL-25 and hepatic steatosis,activation of M2 macrophages and other factors in patients with NAFLD,with the purpose of providing reference value for the progress,diagnosis and treatment of NAFLD.Methods:we selected 87 patients with NAFLD,including 41 patients who met NAFLD with T2 DM,and selected 32 with non-NAFLD,carefully recording their general situation,medical history and other related medical history,drinking history,medication history,measured their height,weight,waist circumference,waist-to-hip ratio(WHR),blood pressure,detected their liver enzyme,blood fat,fasting blood glucose(FBG),Fasting insulin(FINS),hemoglobin A1C(HbA1C),IL-25,and other cytokine levels tested by ELISA,calculate BMI,WHR,Homeostasis model assessment-Insulin resistance(HOMA-IR),Insulin sensitivity index(ISI).Liver biopsies were randomly selected from 10 patients with NAFLD,and Liver biopsies from 6 patients with non-NAFLD who operated,detect the expression of IL-25 and th2 respond reaction reated cytokines mRNA in liver,protein and the expression of IL-25,macrophages surface markers and M2 macrophages surface markers proteins in liver by immunohiistochchemistry/fluorescence.Results:1.The comparison of the baseline characteristics and clinical characteristics among diferent groups1.1 Comparison of the baseline characteristics and clinical characteristics between patients with NAFLD and control groupA total of 119 subjects(69 males)were included in the study,including 87 patients with NAFLD and 32 patients in the control group.The mean age was 48±16years,the maximum was 79 years old,and the youngest was 19 years old.Comparedwith the control group,NAFLD patients were heavier,BMI,waist circumference,hip circumference,WHR,and diastolic blood pressure were higher than the control group;total cholesterol(TC),triglyceride(TG)and low density lipoprotein(LDL)were higher in the patients with NAFLD than in the control group,while high-density lipoprotein(HDL)was lower than the control group;FPG,FINS,HbA1 c,and HOMA-IR were higher in the patients with NAFLD than in the control group,while ISI was lower than the control group.1.2 Comparison of the baseline characteristics and clinical characteristics of patients with different degrees of steatosis in NAFLDCompared with patients with mild steatosis,patients with moderate to severe steatosis were significantly heavier;AST and ALT in patients with moderate to severe steatosis were higher,and there were no significant differences in others.There were no significant differences between the two groups in terms of lipid metabolism and glucose metabolism.1.3 Comparison of the baseline characteristics and clinical characteristics between NAFLD patients and patients with NAFLD combined with T2DMCompared with the simple NAFLD group,patients with NAFLD and T2 DM were older and had higher blood pressure;AKP was significantly increased in patients with NAFLD and T2 DM,and ALB and TP were lower than those in NAFLD group;patients with NAFLD combined with T2 DM group have higher TG and lower HDL;FPG,FINS,HOMA-IR and HbA1 c were higher in NAFLD combined with T2 DM than in simple NAFLD group,and ISI was lower than that in NAFLD group.2.Comparison between serum factors such as IL-25Compared with the control group(n=20),the serum IL-13(P=0.038)was decreased in the NAFLD group(n=68),and the serum levels of IL-4(P=0.21)and IL25(P=0.21)were lower.However,the difference was not statistically significant.There were no significant differences in serum IL-25(P=0.46),IL-13(P=0.9),IL-10(P=0.64),IL-5(P=0.55),IL-4(P=0.49)serum levels between patients with simple steatosis(n=60)and moderate to severe steatosis(n=27).Compared with the simple NAFLD group(n=34),NAFLD combined withT2 DM group(n=34)patients with IL4(P=0.003,IL5(P=0.006),IL13(P=0.000),IL25(P=0.000)Both were higher than the simple NAFLD group.3.The expression of various cytokine mRNA in the liver of patientsCompared with the control group,IL-13(P<0.03),IL-4(P<0.004)mRNA expression levels in the NAFLD group were lower than those in the control group.The expression levels of IL-25(P<0.316)and IL-10(P<0.593)mRNA in the liver of the NAFLD group were lower than those of the control group,but the difference was not statistically significant.The expression of transglutaminase 2(TGM2)(P<0.713)mRNA in NAFLD patients was lower than that in the control group,but the difference was not statistically significant.There was no significant difference in the expression of mannose receptor-1(CD206)(P<0.736)mRNA in the liver.Compared with the control group,the expression level of CD68 mRNA((P<0.021))in the liver of the NAFLD group was significantly higher.4.Comparison of expression of CD68,TGM2,CD206,IL-25 and arg-1 in liverLiver immunohistochemistry/immunofluorescence analysis showed that the expression of Arg-1 protein and IL-25 protein in liver of patients with NAFLD was lower than that of the control group,and the expression of CD68 protein in liver was higher than that of the control group,and with the aggravation of fatty liver degeneration,the liver The expression of arg-1,TGM2 and CD206 and IL-25 was more pronounced and the expression of CD68 was increased.5.Relationship between serum IL-25 and clinical indicatorsSerum IL-25 was positively correlated with serum IL-13(r=0.314 p=0.003)?IL-10(r=0.536 p=0.001)?IL-4(r=0.609 p=0.000)?IL-5(r=0.750 p=0.000)?FPG(r=0.240 p=0.024)? HbA1c(r=0.234 p=0.028);negatively correlated with BMI(r=-0.2 p=0.022)?ALT(r=-0.277 p=0.033)?AST(r=-0.263 p=0.009)?ALB(r=-0.290p=0.006),and not related to other indicators such as blood lipids.Conclusion:IL-25 was negatively correlated with hepatic steatosis and the severity ofinflammation associated with it;positively correlated with M2 macrophage activation.Il-25 and M2 macrophages may have inhibitory effect on NAFLD.
Keywords/Search Tags:Nonalcoholic fatty liver disease, interleukin 25, M2 macrophages
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