论文部分内容阅读
目的探讨核因子-κB(NF-κB)及其抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)在野百合碱(MCT)所致肺动脉高压中的作用及其机制。方法大鼠腹腔注射MCT建立肺动脉高压模型,将58只Wistar大鼠随机分为MCT0组、MCT1W组、MCT2W组、MCT3W组、对照/盐水组、MCT/盐水组和MCT/PDTC组。采用右心导管法测定血流动力学指标,用免疫组化法检测细胞间粘附分子-1(ICAM-1)表达及巨噬细胞浸润情况,用电泳迁移率变动分析法(EMSA法)检测NF-κB活化情况。结果MCT注射后1周开始,大鼠肺组织ICAM-1的表达和巨噬细胞浸润明显增加(P<0.01),2周开始,平均右心室压力升高,右心肥厚指数增加(P<0.01)。与对照/盐水组相比,MCT/盐水组平均右心室压力、右心肥厚指数明显增加,NF-κB活化、ICAM-1表达及巨噬细胞浸润明显增多(P均<0.01)。与MCT/盐水组相比,MCT/PDTC组平均右心室压力、右心肥厚指数明显降低,NF-κB活化、ICAM-1表达及巨噬细胞浸润明显减少(P均<0.01)。结论NF-κB/ICAM-1介导的炎症级联反应参与了MCT诱导的肺动脉高压的发展,PDTC可抑制这一炎症反应,减轻肺动脉高压。
Objective To investigate the role of nuclear factor-κB (NF-κB) and its inhibitor pyrrolidine dithiocarbamate (PDTC) in pulmonary hypertension induced by monocrotaline (MCT) and its mechanism. Methods The model of pulmonary hypertension was established by intraperitoneal injection of MCT. 58 Wistar rats were randomly divided into MCT0 group, MCT1W group, MCT2W group, MCT3W group, control / saline group, MCT / saline group and MCT / PDTC group. The right-heart catheterization was used to measure the hemodynamic parameters. The expression of ICAM-1 and the infiltration of macrophages were detected by immunohistochemical method and detected by electrophoretic mobility shift assay (EMSA) NF-κB activation. Results The expression of ICAM-1 and the infiltration of macrophages in the lung tissue of rats were significantly increased at 1 week after MCT injection (P <0.01). After 2 weeks, mean right ventricular pressure increased and right ventricular hypertrophy index increased (P <0.01) ). Compared with control / saline group, mean right ventricular pressure and right ventricular hypertrophy index were significantly increased in MCT / saline group, NF-κB activation, ICAM-1 expression and macrophage infiltration were significantly increased (all P <0.01). Compared with MCT / saline group, mean right ventricular pressure and right ventricular hypertrophy index were significantly decreased in MCT / PDTC group, NF-κB activation, ICAM-1 expression and macrophage infiltration were significantly decreased (all P <0.01). Conclusion NF-κB / ICAM-1-mediated inflammatory cascade is involved in the development of pulmonary hypertension induced by MCT. PDTC can inhibit this inflammatory response and relieve pulmonary hypertension.