风湿性心脏瓣膜钙化的二尖瓣组织中巨噬细胞和炎性因子表达分析

目的 探讨风湿性心脏瓣膜钙化的二尖瓣组织中巨噬细胞分布规律和相关炎性因子表达情况.方法 收集行二尖瓣置换术的风湿性心脏病患者13例为研究组,同期5例终末期心脏病行心脏移植手术的患者为对照组.收集二尖瓣组织标本,用CD68标记全部巨噬细胞,用iNOS,CD163标记M1,M2型巨噬细胞,观察钙化的二尖瓣组织中巨噬细胞浸润情况,同时观察巨噬细胞相关炎症介质(eNOS,IL-10,Arg-1,巨噬细胞集落刺激因子)在钙化二尖瓣中的表达情况.结果 研究组CD68表达积分高于对照组,差异具有统计学意义(P<0.05),间质和内膜层存在大量巨噬细胞浸润;研究组iNOS阳性的M1型巨噬细胞表达积分高于对照组,差异具有显著统计学意义(P<0.01);研究组CD163阳性的M2型巨噬细胞表达积分低于对照组,差异具有统计学意义(P<0.05);研究组eNOS的表达积分高于对照组,差异具有显著统计学意义(P<0.01);研究组抑炎因子IL-10,Arg-1表达积分低于对照组,差异均具有显著统计学意义(P<0.01);研究组巨噬细胞集落刺激因子的表达量低于对照组,差异具有显著统计学意义(P<0.01).结论 风湿性二尖瓣钙化过程中以M1型巨噬细胞浸润为主,可通过上调eNOS等炎性因子来直接促进炎性反应,通过抑制IL-10等炎性因子来间接促进炎性反应.巨噬细胞集落刺激因子表达下调可减少M1型向M2型转化,并长期维持炎性反应.

Distribution of Macrophage and Expression of Inflammatory Cytokines in Mitral Valve Tissues with Rheumatic Valve Calcification

Objective To investigate the distribution of macrophages and the expression of inflammatory cytokines in mitral valve tissues with rheumatic valve calcification.Method A total of 13 patients with rheumatic heart disease undergoing mitral valve replacement were selected as the study group and a total of 5 patients with end-stage heart disease were enrolled in the study.Mitral valve tissue specimens were collected,all macrophages were labeled with CD68,M1 and M2 macrophages were labeled with iNOS and CD163,and the infiltration of macrophages in calcified mitral valve tissues was observed.The expression of macrophage-associated inflammatory mediators (eNOS,IL-10,Arg-1,macrophage colony stimulating factor) was observed in calcified mitral valve.Results CD68 expression score in the study group was higher than that in the control group and the difference was statistically significant (P<0.05),and there were a lot of endometrial interstitial macrophage infiltration layer;the expression score of iNOS-positive M1 macrophages was higher than that in the control group and the difference was statistically significant (P<0.01);the expression score of CD163-positive M2 macrophages in the study group was lower than that in the control group,with a statistically significant difference (P<0.05).The expression score of eNOS in the study group was higher than that in the control group,showing a statistically significant difference (P<0.01).The expression scores of IL-10 and Arg-1 in the study group were lower than those in the control group,and the difference was statistically significant (P<0.01).The expression score of macrophage colony stimulating factor in the study group was significantly lower than that in the control group (P<0.01).Conclusion Rheumatic mitral valve calcification is characterized by the infiltration of M1 macrophages,in which the inflammation can be directly promoted through the up-regulation of eNOS and other inflammatory factors,and indirectly by inhibiting IL-10 and other inflammatory factors.The down-regulation of macrophage colony-stimulating factor can reduce the transformation from M1 type to M2 type and maintain the inflammatory response for a long time.