摘要
目的从细胞受体和免疫分子水平探讨T2DM内毒素性肺损伤肺局部防御功能减弱的机制。方法雄性Wistar大鼠高糖高脂饲料喂养,小剂量链脲佐菌素(STZ)注射建立T2DM大鼠模型。经尾静脉注射脂多糖(LPS)建立内毒素血症/急性肺损伤大鼠模型。肺泡巨噬细胞(AM)表面CD14表达测定采用免疫组化法,并进行计算机图像分析。放免法检测血清及肺组织匀浆液中TNF-α、IL-6的水平。结果T2DM大鼠AM表面CD14表达和血清TNFα-、IL-6水平明显高于正常对照大鼠(P<0.05)。而经LPS激活后,T2DM及正常对照大鼠AM表面CD14表达及血清、肺组织匀浆液中TNF-α、IL-6水平明显增高(P<0.05),但T2DM组上述指标低于正常对照组,差异有统计学意义(P<0.01)。结论T2DM肺组织的局部防御功能减弱可能与AM经LPS激活后CD14分子上调表达减弱及分泌TNF-α、IL-6能力下降有关。
Objective To investigate the mechanism for weakened pulmonary local immune defensive function at levels of cell receptor and immunomolecule in type 2 diabetes mellitus(T2DM) rats with acute lung injury induced by lipopolysaccharide(LPS). Methods Wistar rats were fed with the diets rich in highsucrose and highlipid. T2DM model was developed by intraperitoneal injection with streptozotocin 35 mg/kg of body weight 1 month after the diet treatment. Murine model of endotoxemia/ acute lung injury was produced by injection LPS(1 mg/kg of body weight) via tail vein. The expression of CD14 on alveolar macrophage(AM) surface was assayed by immunohistochemistry and then analyzed with computer imaging system. Radioimmunoassay was used to determine the levels of TNF-α and IL-6 in serum and pulmonary homogenates. Results The expression of CD14 on AM surface and the levels of TNF-α and IL-6 in serum in T2DM rats without LPS challenge were significantly higher than those in normal control rats(P〈0.05). There was markedly increased average absorbance(A) value of CD14 and the levels of TNF-α and IL-6 in serum and pulmonary homogenates in both normal control rats and T2DM rats after LPS challenge(P〈0.01 ), but the parameters mentioned above in T2DM rats were significantly lower than those in normal control rats after LPS challenge(P〈0.01). Conclusions The expression of CD14 on AM surface and the secretion of TNF-α and IL-6 after LPS challenge are severely decreased in T2DM rats. This might be one of important mechanisms for weakened pulmonary local immune defensive function in T2DM.
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2006年第1期52-55,共4页
Chinese Journal of Diabetes