[1]杨利萍,张友兰,唐凤鸣,等.基于TGFβ1/Smad7通路观察麻黄碱对肺心病大鼠血管内皮结构及功能的影响[J].西部中医药,2022,35(04):48-54.[doi:10.12174/j.issn.2096-9600.2022.04.11]
　YANG Liping,ZHANG Youlan,TANG Fengming,et al.Effects of Ephedrine on Function and Structure of Vascular Endothelium in Pulmonary Heart Disease Rats Based on TGFβ1/Smad7 Signaling Pathway[J].Western Journal of Traditional Chinese Medicine,2022,35(04):48-54.[doi:10.12174/j.issn.2096-9600.2022.04.11]
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基于TGFβ1/Smad7通路观察麻黄碱对肺心病大鼠血管内皮结构及功能的影响
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《西部中医药》[ISSN:2096-9600/CN:62-1204/R]

卷:
35
期数:
2022年04期
页码:
48-54
栏目:
药理研究
出版日期:
2022-04-15

文章信息/Info

Title:
Effects of Ephedrine on Function and Structure of Vascular Endothelium in Pulmonary Heart Disease Rats Based on TGFβ1/Smad7 Signaling Pathway
作者:
杨利萍, 张友兰, 唐凤鸣, 欧扬, 李莹
四川省人民医院温江医院/成都市温江区人民医院,四川 成都 611000
Author(s):
YANG Liping, ZHANG Youlan, TANG Fengming, OU Yang, LI Ying
Wenjiang Hospital of Sichuan Provincial People′s Hospital/Wenjiang District People′s Hospital of Chengdu, Chengdu 611000, China
关键词:
肺心病; 肺动脉高压; 麻黄碱; TGF/Smad7通路; 内皮结构与功能
Keywords:
pulmonary heart disease; pulmonary hypertension; ephedrine; TGF/Smad7 signaling pathway; endothelial structure and function
分类号:
R541.5
DOI:
10.12174/j.issn.2096-9600.2022.04.11
文献标志码:
A
摘要:
目的基于转化生长因子β1（transforming growth factor β1，TGFβ1）/信号转导分子7（signal transduction molecule 7，Smad7）通路观察麻黄碱对肺心病大鼠血管内皮结构及功能的影响。 方法选择12～13周龄的SD大鼠60只，采用随机数字表法分为正常组、模型组、治疗组、抑制剂组，每组15只。正常组注射等体积生理盐水，其他各组大鼠腹腔一次性注射1%野百合碱溶液，构建肺动脉高压大鼠模型。造模后治疗组和抑制剂组大鼠分别每日1次定时以10 mg/kg麻黄碱和SB431542灌胃给药，正常组和模型组给予等剂量生理盐水。连续给药4周后，测定各组大鼠右心室收缩压（right ventricular systolic pressure，RVSP）和肺动脉压（pulmonary artery pressure，PAP），计算右心室肥厚指数（right ventricular hypertrophy index，RVHI），检测血清中一氧化氮（nitric oxide，NO）和血浆中内皮素1（endothelin 1，ET-1）的水平。染色、电镜、TUNEL染色、荧光原位杂交、Western blot检测各组大鼠肺小动脉病理改变、超微结构改变、内皮细胞凋亡、氧化应激指标以及TGFβ1、p-Smad2、p-Smad7 mRNA和蛋白表达情况。 结果与正常组比较，模型组大鼠RVSP、PAP、RVHI、ET-1、ROS和MDA水平、内皮细胞凋亡率，TGFβ1、p-Smad2及p-Smad7的mRNA和蛋白表达均显著升高，NO、SOD和T-AOC水平明显下降，差异均有统计学意义（P＜0.05）；与模型组比较，治疗组、抑制剂组大鼠RVSP、PAP、RVHI、ET-1、ROS和MDA水平、内皮细胞凋亡率，TGFβ1及p-Smad2的mRNA和蛋白表达均显著下降，NO、SOD、T-AOC水平及p-Smad7的mRNA和蛋白表达显著上升，差异均有统计学意义（P＜0.05）；治疗组和抑制剂组比较，各指标间差异无统计学意义（P＞0.05）。 结论麻黄碱对PAH肺动脉血管内皮的保护作用与TGFβ1/Smad7信号通路有关，可能是通过抑制TGFβ1和p-Smad2的表达，上调p-Smad7的表达来实现的。
Abstract:
ObjectiveTo observe the effects of ephedrine on function and structure of vascular endothelium in pulmonary heart disease rats based on TGFβ1/Smad7 signaling pathway. MethodsSixty SD rats aged 12-13 weeks were chosen, and divided into the normal group, the model group, the treatment group and inhibitor group according to random number table method, with 15 rats in each group. Except that the normal group was injected with equal volume of saline, the rats in other groups accepted intraperitoneal injection of 1% monocrotaline solution to prepare rat models with pulmonary arterial hypertension. After modeling, the rats in the treatment group and the inhibitor group were drenched with ephedrine, 10mg/kg, and SB431542 at a fixed time once each day respectively, the normal group and the model group were given the same dose of normal saline. After administrating for four weeks consecutively, to detect RVSP and PAP of the rats in different groups, to calculate RVHI, to measure the levels of NO and ET-1 in the serum. Western blot was used to measure pathological changes of pulmonary arterioles, ultrastructural changes, endothelial cell apoptosis and oxidative stress indexes, the expressions of TGFβ1, p-Smad2, p-Smad7 mRNA and protein after staining, electron microscopy, TUNEL staining and fluorescence in situ hybridization. ResultsCompared with the normal group, the levels of RVSP, PAP, RVHI, ET-1, ROS and MDA, endothelial cell apoptosis rate, the expressions of TGFβ1, p-Smad2, p-Smad7 mRNA and protein rose notably in the model group, the levels of NO, SOD and T-AOC lowered apparently, and the difference had statistical meaning (P<0.05); compared with the model group, the levels of RVSP, PAP, RVHI, ET-1, ROS and MDA, endothelial cell apoptosis rate, the expressions of TGFβ1, p-Smad2 mRNA and protein decreased significantly in the treatment group and the inhibitor group, the levels of NO, SOD and T-AOC, the expressions of p-Smad7 mRNA and protein increased apparently, and the difference showed statistical meaning (P<0.05); the difference had no statistical meaning in the comparisons of the indexes between the treatment group and the inhibitor group (P>0.05). ConclusionProtective effects of ephedrine on PAH pulmonary artery endothelium are related to TGFβ1/Smad7 signaling pathway, which might be realized by inhibiting the expressions of TGFβ1 and p-Smad2 and up regulating the expressions of p-Smad7.

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[1]鲁柏山,梁雨才.丹红注射液联合多索茶碱注射液治疗慢性肺心病60例[J].西部中医药,2016,29(02):113.
　LU Baishan,LIANG Yucai.Treating 60 Patients with Chronic Pulmonary Heart Disease by DanHong Injection and Doxofylline Injection[J].Western Journal of Traditional Chinese Medicine,2016,29(04):113.
[2]郭晓燕,钱家骅,徐向前,等.川芎平喘合剂对COPD相关肺动脉高压大鼠NO、ET-1的影响[J].西部中医药,2018,31(11):14.
　GUO Xiaoyan,QIAN Jiahua,XU Xiangqian,et al.Effects of ChuanXiong Asthma-relieving Mixture on NO and ET-1 of Rat Model with COPD Associated Pulmonary Artery Hypertension[J].Western Journal of Traditional Chinese Medicine,2018,31(04):14.

备注/Memo

备注/Memo:
杨利萍（1973—），女，主治医师。研究方向：呼吸衰竭的诊疗。
更新日期/Last Update: 2022-06-24