[1]马宏恩,王 鑫,季朝红,等.脑钠肽通过环磷酸鸟苷/蛋白激酶G信号通路对高血压降压效果及左心室肥厚逆转作用的机制研究[J].陕西医学杂志,2023,52(10):1308-1312,1318.[doi:DOI:10.3969/j.issn.1000-7377.2023.10.006]
　MA Hongen,WANG Xin,JI Chaohong,et al.Mechanism study of brain natriuretic peptide in reducing blood pressure and reversing left ventricular hypertrophy through cGMP/PKG signaling pathway[J].,2023,52(10):1308-1312,1318.[doi:DOI:10.3969/j.issn.1000-7377.2023.10.006]
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脑钠肽通过环磷酸鸟苷/蛋白激酶G信号通路对高血压降压效果及左心室肥厚逆转作用的机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年10期
页码:
1308-1312,1318
栏目:
基础研究
出版日期:
2023-10-05

文章信息/Info

Title:
Mechanism study of brain natriuretic peptide in reducing blood pressure and reversing left ventricular hypertrophy through cGMP/PKG signaling pathway
作者:
马宏恩; 王 鑫; 季朝红; 张 圆; 魏文扬
(西安市第九医院心血管内科,陕西 西安710054)
Author(s):
MA Hongen; WANG Xin; JI Chaohong; ZHANG Yuan; WEI Wenyang
(Department of Cardiovascular Medicine,Xi'an Ninth Hospital,Xi'an 710054,China)
关键词:
高血压;  左心室肥厚;  脑钠肽;  环磷酸鸟苷/蛋白激酶G信号通路;  氧化应激
Keywords:
High blood pressure;  Left ventricular hypertrophy;  Brain natriuretic peptide;  Cyclic guanosine phosphate/protein kinase G signaling pathway;  Oxidative stress
分类号:
R 544.1
DOI:
DOI:10.3969/j.issn.1000-7377.2023.10.006
文献标志码:
A
摘要:
目的:探讨脑钠肽对高血压的降压效果以及左心室肥厚的改善作用,探究其可能的作用机制。方法:清洁级雄性SD大鼠被分为对照组、模型组、脑钠肽组、脑钠肽+PKG抑制剂(KT5823)组。其中对照组大鼠分离腹主动脉,但并不进行缩窄腹主动脉; 其余组大鼠均采用腹主动脉缩窄法构建高血压左心室肥厚大鼠模型; 脑钠肽组每天通过微型泵以0.05 μg/(kg·min)的速率连续静脉输注脑钠肽; 脑钠肽+KT5823组通过微型泵输注相同剂量脑钠肽的同时以0.01 μg/(kg·min)的速率连续静脉输注PKG抑制剂KT5823。各组大鼠造模前,以及造模(给药)后2、4周时,使用血压计测量大鼠的收缩压,并在造模(给药)后4周处死大鼠,分离心肌组织,称取左心室质量(LVW),测量左胫骨长度(TL),计算LVW/TL比值。使用蛋白免疫印迹法(Western blot)检测各组大鼠心肌组织cGMP依赖性蛋白激酶Ⅰ(PKG-Ⅰ)、转化生长因子β1(TGF-β1)蛋白表达情况; 使用酶联免疫吸附法(ELISA)检测各组大鼠心肌组织血管紧张素Ⅱ(AngⅡ)、Smad家族成员3(Smad3)、Ⅲ型胶原、活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平; 使用马松实验(MASSON)检测各组大鼠心肌组织形态学变化。结果:与对照组比较,模型组大鼠收缩压、LVW/TL比值、心肌组织中TGF-β1、AngⅡ、Smad3、Ⅲ型胶原、ROS、MDA水平显著增加(均P<0.05),而PKG-Ⅰ、SOD水平显著降低(均P<0.05); 与模型组比较,脑钠肽组大鼠收缩压、LVW/TL比值、心肌组织中TGF-β1、AngⅡ、Smad3、Ⅲ型胶原、ROS、MDA水平显著减少(均P<0.05),而PKG-Ⅰ、SOD水平显著上升(均P<0.05); 与脑钠肽组比较,脑钠肽+KT5823组大鼠收缩压、LVW/TL比值、心肌组织中TGF-β1、AngⅡ、Smad3、Ⅲ型胶原、ROS、MDA水平显著增加(均P<0.05),而PKG-Ⅰ、SOD水平显著降低(均P<0.05)。同时KT5823可逆转脑钠肽对模型组大鼠心肌纤维化的改善作用。结论:脑钠肽可通过调控环磷酸鸟苷(cGMP)/环磷酸鸟苷依赖性蛋白激酶(PKG)信号通路降低高血压左心室肥厚大鼠血压,减轻其氧化应激水平,同时改善其左心室肥厚程度。
Abstract:
Objective:To investigate the effect of reducing blood pressure and reversing left ventricular hypertrophy of brain natriuretic peptide,and to explore its possible mechanism.Methods:Clean male SD rats were divided into control group,model group,brain natriuretic peptide group and brain natriuretic peptide+KT5823 group.In the control group,the abdominal aorta was isolated without constriction.Hypertensive left ventricular hypertrophy rat model was established by abdominal aortic coarctation in other groups.The brain natriuretic peptide group received continuous intravenous infusion of brain natriuretic peptide at a rate of 0.05 μg/(kg·min)through a mini-pump every day.In the brain natriuretic peptide+KT5823 group,the same dose of brain natriuretic peptide was infused by mini-pump,and the PKG inhibitor KT5823 was continuously infused intravenously at the rate of 0.01 μg/(kg·min).Systolic blood pressure(SBP)was measured by sphygmomanometer before modeling,2 weeks after modeling(administration)and 4 weeks after modeling(administration).The rats were sacrificed at 4 weeks after modeling(administration),myocardial tissue was isolated,left ventricular mass(LVW)was measured,left tibia length(TL)was measured,and LVW/TL ratio was calculated.Western blot was used to detect the protein expressions of cGMP-dependent protein kinaseⅠ(PKG-Ⅰ)and transforming growth factor-β1(TGF-β1)in myocardial tissue of rats in each group.The levels of angiotensin Ⅱ(AngⅡ),Smad3,collagen type Ⅲ,reactive oxygen species(ROS),malondialdehyde(MDA)and superoxide dismutase(SOD)in myocardial tissue were detected by enzyme-linked immunosorbent assay(ELISA).MASSON test was used to detect the morphology of myocardium in each group.Results:Compared with the control group,the systolic blood pressure,LVW/TL ratio,the levels of TGF-β1,AngⅡ,Smad3,collagen type Ⅲ,ROS and MDA in the model group were significantly increased(all P<0.05),while the levels of PKG-Ⅰ and SOD were significantly decreased(all P<0.05).Compared with the model group,the systolic blood pressure,LVW/TL ratio,and the levels of TGF-β1,AngⅡ,Smad3,collagen type Ⅲ,ROS and MDA in the brain natriuretic peptide group were significantly decreased(all P<0.05),while the levels of PKG-Ⅰ and SOD increased significantly(all P<0.05).Compared with brain natriuretic peptide group,systolic blood pressure,LVW/TL ratio,and the levels of TGF-β1,AngⅡ,Smad3,collagen type Ⅲ,ROS and MDA in myocardial tissue of rats in brain natriuretic peptide+KT5823 group were significantly increased(all P<0.05),while the levels of PKG-Ⅰ and SOD were significantly decreased(all P<0.05).KT5823 can reverse the inhibitory effect of brain natriuretic peptide on myocardial fibrosis in model group rats.Conclusion:Brain natriuretic peptide can reduce blood pressure,reduce oxidative stress and reverse left ventricular hypertrophy in hypertensive rats by regulating cGMP/PKG signaling pathway.

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备注/Memo

备注/Memo:
基金项目:陕西省自然科学基础研究计划项目(2022JM-580); 西安市卫生健康委员会科学研究计划项目(2020YB23)
更新日期/Last Update: 2023-10-07