甜菜碱调控RhoA/ROCK抑制野百合碱致大鼠肺动脉高压  

Betaine inhibits monocrotaline induced pulmonary hypertension in rats by regulating RhoA/ROCK protein expression

作　　者：张波涛[1] 王雅蓉 张婷 李璐 ZHANG Botao;WANG Yarong;ZHANG Ting;LI Lu(General Hospital,Ningxia Medical University,Yinchuan 750004,China;不详)

机构地区：[1]宁夏医科大学总医院,银川750004 [2]宁夏武警医院,银川750004

出　　处：《实用医学杂志》2023年第15期1876-1880,共5页The Journal of Practical Medicine

基　　金：宁夏回族自治区重点研发计划项目(编号:2020BEG03040);宁夏医科大学科学研究基金资助项目(编号:81160403)。

摘　　要：目的 探讨甜菜碱对野百合碱(monocrotaline,MCT)诱导的大鼠肺动脉高压(pulmonary arterial hypertension,PAH)RhoA/ROCK通路蛋白表达的影响。方法 将72只SD(Sprague Dawley)大鼠随机分为:对照组、MCT组(50 mg/kg)、西地那非(30 mg/kg)组、甜菜碱低、中和高(100、200、400 mg/kg)剂量组。MCT组大鼠造模成功后第22天开始给药,于第41天检测大鼠右心室收缩压及右心室肥厚指数、脏器指数指标。采用Western blot法分别测定大鼠心肌和肺组织中RhoA、ROCK1和ROCK2蛋白的表达。结果 与MCT组比较,甜菜碱(400 mg/kg)和西地那非(30 mg/kg)均可显著降低大鼠平均肺动脉压(mPAP)、右心室收缩压(RVSP)和右室肥厚指数(RVHI)(P <0.01)。与对照组相比,MCT组中肺组织和心组织RhoA、ROCK1、ROCK2蛋白表达上调,但甜菜碱(400 mg/kg)组抑制其表达水平的增加(P <0.05)。结论 甜菜碱可降低MCT诱导大鼠的肺动脉高压,其机制可能与下调大鼠肺组织和心肌组织RhoA/ROCK通路的RhoA、ROCK1和ROCK2蛋白的表达有关。Objective To investigate the effect of bethaneline on expression of rhoA/ROCK pathway protein in pulmonary arterial hypertension(PAH) induced by monocrotaline(MCT) in rats.Methods 72 SD(Sprague Dawley) rats were randomly divided into control group,MCT(50 mg/kg) group,sildenafil(30 mg/kg) group and low,medium,high(100,200,400 mg/kg) group depending on betaine level.Monocrotaline group was adminstered on the 22^(nd) day after successful modeling,and then the right ventricular systolic pressure,right ventricular hypertrophy index and visceral index were measured on the 41st day.The expressions of RhoA,Rock1 and Rock2 in the rat myocardial and lung homogenates were detected by Western blot.Results Compared with MCT,both betaine(400 mg/kg) and sildenafil(30 mg/kg) significantly reduced the mean pulmonary artery pressure(mPAP),right ventricular systolic pressure(RVSP) and right ventricular hypertrophy index(RVHI)(P<0.01).Lung and cardiac tissue expression of RhoA,ROCK1,and ROCK2 proteins were upregulated in the MCT group as compared with the control group,but the expression was significantly suppressed in the betaine group(400 mg/kg)(P<0.05).Compared with the control group,the expression of RhoA,ROCK1 and ROCK2 proteins in the lung and heart tissues of the MCT group was up-regulated,but the expression was significantly inhibited in the betaine group(400 mg/kg)(P<0.05).Conclusion Betaine can reduce monocrotaline induced pulmonary hypertension in rats.It is speculated that its mechanism may be related to the down-regulated expression of RhoA,ROCK1 and ROCK2in rat lung and myocardium through the RhoA/ROCK pathway.

关 键 词：甜菜碱 肺动脉高压 右心室重构 RhoA/ROCK 野百合碱 

分 类 号：R541.5[医药卫生—心血管疾病]