烧伤合并内毒素血症骨髓粒单系造血变化及其机制的探讨

Changes and mechanism of bone marrow granulopoiesis after burns combined with endotoxemia in mice

目的 :探讨烧伤合并内毒素血症骨髓粒单系造血变化及其机制。方法 :采用细胞计数和细胞培养观测2 0 %总体表面积 度烧伤合并内毒素 (按体重 1μg/ g)腹腔注射后 (烧注组 ) 1周内小鼠外周血粒细胞和单核细胞总数及骨髓粒巨噬细胞集落形成单位 (CFU GM)的动态变化 ;同时用免疫组织化学和放射免疫法检测骨髓细胞环氧化酶 2 (COX 2 )和转化生长因子 β1 (TGFβ1 )表达及骨髓细胞上清前列腺素 E2 (PGE2 )含量变化。结果 :烧注后 6小时内外周血粒细胞和单核细胞总数、骨髓 CFU GM略增多 ,以后逐渐减少 ,外周血粒细胞和单核细胞总数在 1～ 5日、骨髓 CFU GM在 12小时～ 5日显著低于正常对照组。烧注后 1、3日骨髓细胞COX 2和 TGFβ1 表达明显增强 ,12小时～ 5日 PGE2 显著高于正常对照组 ,PGE2 与 CFU GM呈显著负相关。结论 :烧伤合并内毒素血症骨髓粒单系造血抑制 ;PGE2 可能在烧伤合并内毒素血症骨髓粒单系抑制中起重要作用 ;TGFβ1 可能也是粒单系抑制的原因之一。

Objective:To investigate changes and mechanism of bone marrow granulopoiesis after burns combined with endotoxemia in mice.Methods:Circulating granulocytes and monocytes were counted and colony forming unitgranulocyte/macrophage(CFUGM) culture was performed in mice sustained 20% total body surface area(TBSA) fullthickness burn injury combined with endotoxin (LPS,1 μg/g body weight) injection during a period of 7 days.Meanwhile,the expressions of cyclooxygenase(COX2) and transforming growth factorβ 1(TGFβ 1) of blood mononuclear cell(BMNC) were determined with immunohistochemistry,and levels of prostaglandin E 2(PGE 2) in BMNC supernatant were determined with radioimmunoassay.Results:Circulating granulocytes,monocytes and bone marrow CFUGM increased slightly within 6 hours after burn injury combined with LPS injection,then decreased gradually.Circulating granulocytes and monocytes were significantly lower from day 1 to day 5,and bone marrow CFUGM were significantly lower from 12th hour to day 5 when compared with those in control.The expression of COX2 and TGFβ 1 in BMNC were increased from day 1 to day 3 after burns combined with LPS injection.PGE 2 levels in BMNC supernatant increased from 12th hour to day 5.Moreover,negative correlation was found between PGE 2 and CFUGM.Conclusions:Bone marrow granulopoiesis was suppressed after burns combined with endotoxemia,and PGE 2 might play a pivotal role in the pathophysiological process.TGFβ 1 might be one of the contributing factors in granulopoiesis suppression.