慢性低氧高二氧化碳诱导肺动脉高压小鼠肺组织白细胞介素6的表达

目的: 通过观察慢性低氧(O₂)高二氧化碳(CO₂)小鼠肺组织白细胞介素6(interleukin 6, IL-6)的表达水平变化,探讨其在慢性低O₂高CO₂肺动脉高压形成过程中的作用。方法: 16只SPF级雄性C57BL/6小鼠按随机数字表法随机分为正常对照组和低氧高CO₂组,每组8只。低氧高CO₂组置于常压低O₂高CO₂舱内, O₂浓度9%~10%,CO₂浓度5%~6%,每天8h,每周6 d,共4周。4周后,分离右心室和左心室加室间隔,计算右心肥大指数,肺组织行苏木精-伊红(HE)染色,光学显微镜观测肺血管结构变化,Image-Pro Plus 6.0图像分析系统测量管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%)。免疫组织化学方法观测肺动脉中IL-6蛋白的表达,ELISA测定肺组织匀浆中IL-6蛋白浓度;RT-PCR检测肺组织中IL-6 mRNA表达。结果: 低氧高CO₂组与对照组相比:(1)右心肥大指数、WT%和WA%显著提高(P<0.01);(2)肺组织中IL-6的蛋白表达水平显著提高(P<0.01);(3)肺组织中IL-6 mRNA表达水平明显提高(P<0.05)。结论: 在慢性低氧高二氧化碳环境中,小鼠的肺组织IL-6水平升高伴随肺血管壁肌层增厚和管腔狭窄,这可能与小鼠的肺动脉高压发生、发展有关。

Changes of interleukin-6 in pulmonary hypertension mice induced by chronic hypoxic-hypercapnia

AIM: To investigated the changes of interleukin-6(IL-6) in the pulmonary hypertension mice induced by chronic hypoxic hypercapnia.METHODS: Sixteen male C57BL/6 mice were randomly divided into 2 groups(8 mice in each group): normal control group and chronic hypoxic hypercapnia group.The mice in chronic hypoxic hypercapnia group were placed in a sealed chamber where O2 concentration was kept at 9%~11%,and the CO2 concentration at 5% ~6%,8 h a day,6 days a week for 4 weeks.The right ventricular(RV) weight,the weight of left ventricle plus ventricular septum(LV+S) were measured and right ventricular hypertrophy index was calculated.The structural changes of the pulmonary arteries were assessed by the method of histology with HE staining.The vessel wall diameter/total diameter(WT%) and the vessel wall area/total area(WA%) were analyzed by Image-Pro Plus 6.0 software.The protein expression of IL-6 in the lungs of the mice was determined by immunohistochemistry and ELISA,and the mRNA expression of IL-6 in the lungs was determined by RT-PCR.RESULTS: Compared with control group,RV/(LV+S),MT%,MA% and the expression of IL-6 at mRNA and protein levels were significantly increased in chronic hypoxic hypercapnia group.CONCLUSION: In the environment of chronic hypoxia and hypercapnia,the expression of interleukin-6 was elevated in mouse lungs,which may closely related to the development of pulmonary hypertension.