COX抑制剂对压力超负荷性心肌肥厚大鼠心室重构的作用

Effects of COX Inhibitors on Ventricular Remodeling in Rats with Pressure Overload Myocardial Hypertrophy

目的 研究环氧化酶(COX)抑制剂阿司匹林、塞来昔布对压力超负荷性心肌肥厚大鼠心室重构的影响及机制。方法 选取200±20g SPF级SD大鼠,通过腹主动脉缩窄法建立心肌肥厚大鼠模型,随机分为正常对照组、模型组、模型+阿司匹林组、模型+塞来昔布组。正常对照组和模型组以0.9%氯化钠溶液2ml/100g灌胃,阿司匹林组10mg/100g灌胃,塞来昔布组1.8mg/100g灌胃,分别灌胃至第8、10、12、14周取血浆和心肌组织。计算左心室质量指数,HE染色观察左心室心肌细胞形态,Masson染色观察左心室胶原纤维的变化,ELISA法检测血浆炎性因子TNF-α、IL-10的含量,免疫组化检测相关蛋白Notch1、Hey2的表达。结果 与正常对照组比较,模型组心肌细胞排列紊乱,胶原纤维增生,左心室质量指数、细胞短轴直径、血浆炎性细胞因子TNF-α、IL-10含量及Notch1和Hey2的蛋白含量显著升高,且随着时间的变化,模型组的各项检测指标逐渐增加。与模型组比较,阿司匹林组及塞来昔布组的心肌细胞排列稍显整齐,左心室质量指数、细胞短轴直径、胶原纤维、血浆炎性细胞因子TNF-α、IL-10含量显著下降,且随时间的延长,加药的两组上述指标整体趋势逐渐降低,Notch1和Hey2的蛋白表达量随时间变化先升高后下降。结论 环氧化酶抑制剂具有减轻压力超负荷性心肌肥厚大鼠心室重构的作用,这可能与Notch1信号通路蛋白的调节及炎症因子含量降低相关。并且在短期内,阿司匹林发挥作用较早,长时间后,塞来昔布的作用逐渐显现,效果同阿司匹林相似。

Objective To study the effect and mechanism of cyclooxygenase inhibitor aspirin and celecoxib on ventricular remodeling in pressure-overloaded myocardial hypertrophy rats.Methods SD rats of 200±20 g SPF grade were selected,and rat models of myocardial hypertrophy were established by abdominal aortic coarctation method.They were randomly divided into normal control group,model group,model + aspirin group,model + celecoxib group.Normal control group and model group were intragastrically administered with normal saline 2 ml/100 g,aspirin group 10 mg/100 g,and celecoxib group 1.8 mg/100 g by intragastric administration until the 8 th,10 th,12 th,and 14 th weeks,respectively.Plasma and myocardial tissue were collected weekly.The left ventricular mass index was calculated.HE staining was used to observe the morphology of left ventricular cardiomyocytes.Masson staining was used to observe the changes of left ventricular collagen fibers.The Elisa method was used to detect the plasma inflammatory factors TNF-Plasma and myocardiImmunohistochemical detection of the expression of related proteins Notch1 and Hey2 was performed.Results Compared with the normal control group,the cardiomyocytes of the model group were arranged disorderly,collagen fibers proliferated,left ventricular mass index,cell short axis diameter,plasma inflammatory factors TNF-α and IL-10,rotein content of Notch1 and Hey2 significantly increased.With the change of time,the detection indicators of the model group gradually increased.Compared with the model group,the arrangement of cardiomyocytes in the aspirin group and celecoxib group was slightly neater,and the left ventricular mass index,cell short axis diameter,collagen fibers,plasma inflammatory factors TNF-α and IL-10 levels were significantly decreased.With the prolongation of time,the overall trend of the above indicators in the two groups of drug-added groups gradually decreased.The protein expressions of Notch1 and Hey2 first increased and then decreased with time.Conclusion Cyclooxygenase inhibitors can reduce ventricular remodeling in rats with pressure overload myocardial hypertrophy,which may be related to the regulation of Notch1 signaling pathway proteins and the reduction of inflammatory factors.And in the short term,aspirin takes effect earlier,after a long time,the effect of celecoxib gradually appears,and the effect is similar to that of aspirin.