巨噬细胞表型转换在NAFLD发生过程中的可能作用

摘要

目的 探讨非酒精性脂肪性肝病(NAFLD)患者网膜脂肪、皮下脂肪中巨噬细胞数量及不同表型,以及其与NAFLD严重程度的关系及意义.方法 选择2012年4～12月于第三军医大学大坪医院野战外科研究所住院的NAFLD伴单纯性胆囊结石患者27例(NAFLD组),以及同期单纯性胆囊结石但排除NAFLD及其他一切肝病的肝功能正常的单纯性胆囊结石患者28例(非NAFLD组).对两组患者的年龄、性别、体质量指数(BMI)、腹围、血糖、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、胰岛素抵抗指数(HOMA-IR)、胰岛素、游离脂肪酸(FFA)进行比较.使用CD68标记巨噬细胞、CD11C标记M1亚群巨噬细胞,CD206标记M2亚群巨噬细胞,免疫组织化学染色检测其网膜脂肪组织、皮下脂肪组织的巨噬细胞及M1亚群,M2亚群数量.结果 NAFLD组和非NAFLD组的年龄、性别、腹围、血糖、ALT、AST、总胆红素(TB)、FFA比较,差异无统计学意义(P>0.05).而BMI、胰岛素、HOMA指数、TG在NAFLD组明显高于非NAFLD组,差异有统计学意义(P<0.05).在NAFLD组中,网膜脂肪M1亚群、皮下的脂肪M1亚群及M2亚群巨噬细胞数量明显增高,与非NAFLD组比较,差异有统计学意义(P<0.01),三者与NAFLD活动度积分(NAS)评分呈正相关(r=0.465、r=0.657、r=0.496,P<0.05).其中网膜及皮下均以M1亚群巨噬细胞增高明显(P<0.01).网膜及皮下脂肪组织的M1/M2在NAFLD组中较非NAFLD组明显增高,差异有统计学意义(P<0.01),但与NAS评分相关不显著(r=0.168、r=0.242,P>0.05).结论 NAFLD患者存在胰岛素抵抗及血脂代谢紊乱,网膜脂肪及皮下脂肪中的巨噬细胞数量及其表型转换可能参与了NAFLD的疾病进展.%Objective To research the number of macrophage and macrophage phenotype transition in epiploic adipose tissue and subcutaneous adipose tissue in non-alcoholic fatty liver disease (NAFLD ) and their relation with the severity of NAFLD and signifi -cance .Methods 27 cases of NAFLD complicated with simple cholelithiasis admitted to the Daping Hospital affiliated to Third Mill -tary Medical University from April to December 2012 were selected as the NAFLD group .Contemporaneous 28 cases of simple cholelithiasis excluding NAFLD and other liver disease with normal liver function were used as the non-NAFLD group .Age ,sex ,BMI, abdominal circumference ,glucose ,ALT ,AST ,TG ,H0M A -IR ,and FFA were compared between the two groups .CD68 was adopted as the macrophage marker ,CDllc as the Mi marker and CD206 as the M2 marker .The number of macrophages ,M1 and M2 subgroups in epiploic adipose tissue and subcutaneous adipose tissue was detected by immunohistochemical staining .Results There were no statistical differences in age ,sex ,abdominal circumference ,glucose ,ALT ,AST and FFA between the NAFLD group and the non-NAFLD group(P>0 .05) .But ,BMI,insulin ,HOM A-IR and TG in the NAFLD group were obviously higher than those in the non-NAFLD group with statistical difference (P<0 .05) .The number of Mi subgroup in epiploic adipose tissue and subcutaneous adipose tissue in the NAFLD group was increased (P<0 .01) and the number of M2 in subcutaneous adipose tissue was also increased difference showing statistical significance compared with the non - NAFLD group (P<0 .01) .A significant positive correlation was found between NAS and M 1 in epiploic adipose tissue and subcutaneous adipose tissue and M 2 in epiploic adipose tissue (r=0 .496 ,r=0 .465 ,r=0 .657 ,P<0 .01) .The number of M1 in epiploic adipose tissue and subcutaneous adipose tissue were remarkably increased(P<0.01).And M1/M2 ratio in epiploic adipose tissue and subcutaneous adipose tissue was also increased in NAFLD group(P<0.01).But there was no correlation between M1/M2 ratio and NAS (r=0 .168 ,r=0 .242 ,P>0 .05) .Conclusion Insulin resistance and lipid metabolism disorder exist in the patients with NAFLD .The number of macrophages and macrophage phenotype transition in epiploic adipose tissue and subcutaneous adipose tissue may participate in the development of NAFLD .