摘要
目的探讨葡萄籽原花青素(grape seed proanthocyanidins,GSP)对苯肾上腺素(phenylephrine,PE)诱导的乳鼠心肌肥大的保护作用及其机制。方法采用PE(20μmol·L^(−1))刺激48 h建立乳鼠心肌肥大模型,分为正常对照组、模型组和GSP低、中、高剂量组(10,20,50μmol·L^(−1))。持续给药48 h后,采用Image J测定心肌细胞面积,Western blotting检测心钠素和β-肌凝蛋白重链的表达。后续实验分组:正常对照组、模型组、GSP阴性对照组、GSP中剂量组,采用荧光探针DCFDA检测活性氧含量,采用试剂盒分别检测细胞内超氧化物歧化酶活性(superoxide dismutase,SOD)、丙二醛含量、上清液乳酸脱氢酶活性,Western blotting检测RhoA蛋白和ROCK活性。结果与模型组相比,GSP干预能够明显降低心肌细胞面积(P<0.05),减少肥大基因心钠素和β-肌凝蛋白重链的表达(P<0.05),并且降低活性氧荧光含量(P<0.05),升高SOD,明显降低丙二醛以及乳酸脱氢酶活性(P<0.05),明显抑制RhoA蛋白和ROCK活性(P<0.05)。结论GSP对心肌肥大的保护作用与抑制活性氧、RhoA/ROCK信号通路活化有关。
OBJECTIVE To study the protective effect and mechanism of grape seed proanthocyanidins(GSP)on phenylephrine(PE)-induced cardiac hypertrophy in neonatal rats.METHODS A model of neonatal cardiac hypertrophy was established by PE(20μmol·L^(−1))stimulation for 48 h,which was divided into normal control group,model group,GSP low,medium,and high dose group(10,20,50μmol·L^(−1)).After 48 h of continuous administration,Image J was used to measure the area of cells,Western blotting was used to detect the expression of atrial natriuretic peptide(ANP)andβ-myosin heavy chain(β-MHC).Subsequent experimental groups:normal control group,model group,GSP negative control group,GSP medium dose group,fluorescent probe DCFDA was used to detect reactive oxygen species(ROS)content,kits were used to detect intracellular superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,lactate dehydrogenase(LDH)activity of supernatant,Western blotting was used to detect RhoA protein and ROCK activity.RESULTS Compared with control group,GSP intervention could significantly reduce the area of cardiomyocytes(P<0.05),reduce the expression of hypertrophic genes ANP andβ-MHC(P<0.05),and reduce the fluorescence content of ROS(P<0.05),improve SOD activity,reduce MDA content and LDH activity(P<0.05),and significantly inhibit RhoA protein and ROCK activity(P<0.05).CONCLUSION The protective effect of GSP on cardiac hypertrophy is related to the inhibition of ROS and RhoA/ROCK signaling pathway.
作者
丁文文
夏鸿
周静
缪园欣
DING Wenwen;XIA Hong;ZHOU Jing;MIAO Yuanxin(Jingchu University of Technology,School of Medical,Jingmen 448000,China;Jingchu University of Technology,School of Biological Engineering,Jingmen 448000,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2021年第15期1820-1825,共6页
Chinese Journal of Modern Applied Pharmacy
基金
荆楚理工学院校级重点项目(ZD202001)
湖北省教育厅中青年人才项目(Q20204305)
湖北省高等学校优秀中青年科技创新团队项目(T201819)。
关键词
心肌肥大
原花青素
活性氧
RHOA
ROCK
cardiac hypertrophy
proanthocyanidins
reactive oxygen species(ROS)
RhoA
ROCK
