粉防己碱对肺动脉高压大鼠中NLRP3炎性小体表达研究

Impact of the NLRP3inflammasome on tetrandrine in rats with pulmonary arterial hypertension

目的:研究肺动脉高压大鼠中NLRP3炎性小体的表达情况,探究粉防己碱对肺动脉高压的保护作用。方法:36只雄性SD大鼠,随机分为3组:正常对照组(control)、肺动脉高压组(MCT)、粉防己碱组(Tet)。对照组单剂量给予0.9%氯化钠腹腔注射,其余两组单剂量给予野百合碱腹腔注射后正常饲养21d;而后Tet组每天给予粉防己碱药物灌胃,其余两组则每天给予0.9%氯化钠灌胃21d后留取组织标本,测量肺动脉压力(右室收缩压,right ventricular systolic pressure,RVSP),计算右心室/(左心室+心室壁)[RV/(LV+S)]比值,行HE染色观测各组形态学变化,免疫组化及western blot检测各组NLRP3、caspase-1及白细胞介素-1β(IL-1β)的表达水平。结果:(1)与对照组相比,MCT及Tet组RVSP、RV/(LV+S)值均明显增高(P<0.05);与MCT组相比,Tet组又明显下降(P<0.05)。(2)病理组织学检测结果显示,粉防己碱可减轻PAH模型大鼠肺小动脉内膜增生,减少肺组织炎性细胞浸润;(3)免疫组化及western blot结果显示,粉防己碱可抑制NLRP3、caspase-1、IL-1β的表达。结论:粉防己碱可以抑制NLRP3炎性小体的活化,减轻肺动脉高压大鼠肺组织的炎性浸润,对肺动脉高压具有一定的逆转作用。

Objective：To investigate expression of the NLRP3 inflammasome in pulmonary arterial hypertension rats and explore the protective effect of tetrandrine on pulmonary arterial hypertension.Method：A toll of 36 male Sprague-Dawley（SD）rats were randomly and equally devided into 3 groups：control group,MCT group and Tet group.The control group was given intraperitoneal injection with normal saline;the others were given intraperitoneal injection with monocrotaline（MCT）to induce PAH,then given irrigation with saline and tetrandrine respectively,from day 21 to day 42.Right ventricular systolic pressure（RVSP）,right ventricular hypertrophy index（RV/（LV＋S））were measured and compared among all groups.HE staining was used to observe the morphological changes of each group.Expression of NLRP3,caspase-1 and IL-1βwere detected by immunohistochemistry and western blot.Result：（1）Compared with control group,RVSP and RV/（LV ＋ S）were significantly increased in MCT and Tet groups（P〈0.05）;While compared with MCT group,Tet group was significantly decreased（P〈0.05）.（2） Histopathological examination showed that Tet could reduce the pulmonary arterial hyperplasia of PAH rats and reduce the infiltration of inflammatory cells in lung tissue.（3）Results of immunohistochemistry and western blot showed that Tet reduced the expression of NLRP3,caspase-1 and IL-1β.Conclusion：Tetrandrine could inhibit the activation of NLRP3 inflammasome,reduce the inflammatory infiltration of lung tissue in pulmonary hypertension rats,and have a certain reversal effect on pulmonary hypertension.