野百合碱对大鼠右心室心肌肥厚功能及规范性瞬时感受器电位6表达水平的影响

摘要

目的探讨腹腔注射野百合碱（ MCT ）对大鼠右心室心肌肥厚功能和规范性瞬时感受器电位6（TRPC6）表达水平的影响。方法采用随机数字表法将大鼠分为对照组（CON组）和MCT给药模型组（MCT组），各25只。CON组大鼠置于常压和正常氧浓度（21%）饲养箱中饲养3周，MCT组大鼠以2% MCT 60 mg/kg一次性腹腔注射，后常规饲养3周。记录两组大鼠右心室收缩压（ RVSP）、心率（ HR）、右心室内压力最大上升/下降速率（ RV ± dp/dtmax）、平均动脉压（ MAP）以及右心室肥大指数（ RVMI）。HE染色观察两组大鼠右心室心肌组织形态。并采用实时定量PCR（ RT-PCR）检测TRPC6 mRNA表达水平，采用Western blotting方法检测TRPC6蛋白表达水平。结果饲养3周后，CON组大鼠死亡1只，MCT组大鼠死亡7只。MCT组和MCT组mSAP和HR比较，差异无统计学意义（P>0.05）；MCT组RVSP、RVMI、RV﹢dp/dtmax高于CON组，RV-dp/dtmax低于CON组（P<0.05）。HE染色可见CON组大鼠右心室心肌细胞排列有序，胞核清晰；MCT组右心室心肌纤维粗大，细胞内肌原纤维数量增多，心肌纤维排列紊乱，细胞核深染，形状不整。CON组右心室心肌组织TRPC6 mRNA表达水平为（1.00±0.51），低于MCT组的（2.49±0.96）（t=-3.33，P<0.05）。CON组右心室心肌组织TRPC6蛋白表达水平为（1.00±0.46），低于MCT组的（2.90±0.32）（t=14.99，P<0.05）。结论 MCT可诱导SD大鼠产生右心室心肌肥大，并显著上调右心室心肌细胞编码TRPC6 mRNA和蛋白的表达水平，TRPC6可能参与右心室心肌肥大的发生发展。%Objective To discuss the effect of intraperitoneal injection of monocrotaline( MCT) on right ventricular hypertrophy function and expression of canonical transient receptor potential 6 ( TRPC6 )in rats. Methods The rats were ran-domly divided into control group and MCT group,with each group 25 cases. The control group was raised for three weeks with nor-mal atmospheric pressure and oxygen concentration(21%),while the MCT group was given single intraperitoneal injection of 60 mg/kg 2% MCT,and then was raised for three weeks. The right ventricular systolic pressure( RVSP),heart rate( HR),right ventricular pressure maximum rate of rise( RV ± dp/dtmax),mean systemic arterial pressure( MAP) and right ventricular mass index(RVMI). The tissue form of right ventricular myocardium were observed by HE staining,and the expression of TRPC6 mRNA was detected by RT-PCR,and the expression of TRPC6 protein was detected by Western blotting. Results After raising for three weeks,one rat died in the control group,and seven died in the MCT group. The mSAP and HR of the two groups showed no statistically significant difference(P>0. 05). The RVSP,RVMI and RV﹢dp/dtmax of the MCT group were higher than the control group,but the RV-dp/dtmax was lower than the control group(P<0. 05). HE staining showed that the myocardial cells in the control group had ordered arrangement with clear nuclei,while in the MCT group,the cardiac muscle fiber of the right ventricle was thick, and the number of intracellular myofibrils was increased, with disordered arrangement and deeply stained and irregular nuclei. The expression of TRPC6 mRNA in the right ventricular myocardium in the control group was(1. 00 ±0. 51),lower than that of the MCT group(2. 49 ±0. 96)(t= -3. 33,P<0. 05). The expression of TRPC6 protein in the right ventricular myocardium in the control group was(1.00 ±0.46),lower than that of the MCT group(2.90 ±0.32)(t=14. 99,P<0. 05). Conclusion MCT can induce right ventricular hypertrophy in SD rats,and can significantly up-regulate the TRPC6 mRNA and protein expression,indicating that the TRPC6 may be involved in the occurrence and development of right ventricular hypertrophy.