中文摘要：

目的观察风湿性心脏瓣膜病钙化的二尖瓣组织中巨噬细胞及其亚型的分布规律以及相关炎性因子的表达情况。方法收集15例风湿性心脏瓣膜病患者的钙化二尖瓣组织作为实验组，7例终末期心肌病患者的二尖瓣组织作为对照组。用CD68、诱导型一氧化氮合酶（iNOS）和CD163分别标记非特异性、M1和M2型巨噬细胞，观察其在钙化的二尖瓣组织中的浸润情况；观察内皮型一氧化氮合酶（eNOS）、IL-10、Arg-1以及巨噬细胞集落刺激因子（M-CSF）在钙化的二尖瓣中的表达。结果与对照组相比，实验组瓣膜中有大量的新生微血管形成。实验组中CD68阳性的巨噬细胞较对照组增多（积分，下同：4．2±2．0比3．2±2．3；Z=-3．981，P=0．000）。实验组iNOS阳性的M1型巨噬细胞浸润较对照组明显增多（3．4±1．7比1．2±1．0；Z=-4．015，P=0．000）。实验组CD163阳性的M2型巨噬细胞浸润较对照组明显减少（1．2±1．0比2．3±1．8；Z=-8．602，P=0．000）。在炎症介质表达方面，实验组中eNOS表达量高于对照组（4．9±1．1比1．8±1．1），而Arg-1及IL-10低于对照组（1．0±1．0比3．3±1．3，2．1±1．2比g．9±1．4）（Z=-8．867～-5．344，P=0．000）；实验组M—CSF的表达低于对照组（2．0±1．4比4．3±0．9；Z=-2．741，P=0．006）。结论风湿性心脏瓣膜病中二尖瓣钙化的病变过程是以M1型巨噬细胞的浸润为主。它可能通过上调eNOS等炎性因子的表达发挥直接致炎作用，而通过抑制IL-10、Arg-1的表达发挥间接致炎作用。M—CSF的表达抑制则可能减少M1型巨噬细胞向M2型巨噬细胞的转化，使炎症反应长期维持。

英文摘要：

Objective To investigate whether valvular expression of macrophage and its subsets and correlative cytokines of mitral valve are altered in patients with rheumatic valvular disease. Methods The mitral valvular leaflets of 15 rheumatic valvular disease patients were included as the test group, and 7 patients of terminal stage cardiomyopathy as the control. The immunostain of CD68, inducible nitric oxide synthase （iNOS） and CD163 were applied to mark the total maerophages, M1 and M2, respectively. The expression of endothelial nitric oxide synthase （eNOS）, IL-10, Arg-1, macrophage-colony stimulating factor （M-CSF） were compared respectively in two groups. Results The angiogenesis was enormous in the test, whereas the cell proliferation was scanty. Compared with the control, CD68 positive macrophages were markly expressed in the test （4. 2 ± 2. 0 vs. 3.2 ± 2. 3 ; Z = - 3. 981, P = 0. 000 ）, also the iNOS positive M1 subsets （3.4 ± 1.7 vs. 1.2 ± 1.0; Z = -4. 015, P =0. 000）. The expression level of CD163 positive macrophages was lower in the test （ 1.2 ± 1.0 vs. 2. 3 ± 1.8 ; Z = - 8. 602, P = 0. 000）. The expression of eNOS was higher in the rheumatic valve disease （ 4. 9 ± 1.1 vs. 1.8 ± 1.1 ） , but the expression levels of Arg-1 （ 1.0 ± 1.0 vs. 3.3 ± 1.3 ） and IL-10 （2. 1 ± 1.2 vs. 4. 9 ±1.4） were lower （ Z = - 8. 867 to -5. 344,P =0. 000）. The expression of M-CSF was lower in test （2.0 ±1.4 vs. 4. 3 ±0. 9; Z = -2. 741, P = 0. 006）. Conclusions The infiltration of M1 macrophages plays an important role in the progression of rheumatic mitral valve disease. It fulfills the pro-inflammation by up-regulating the expression of eNOS. Inversely, it suppresses the expression of IL-10, Arg-1 to relieve the inflammatory action. In according withthe down-regulated level of M-CSF, the polarization from M1 macrophages into M2 is depressed, and the inflammation induced by M1 is sustained.