[Effects of maslinic acid on isoproterenol-induced myocardial fibrosis in mice].

心肌纤维化 纤维化 化学 心脏纤维化 生理盐水 内科学 内分泌学 污渍 医学 生物化学 基因
作者
Zhigang Guo,Di Fan,F Y Liu,Chun‐Yan Kong,Qi Tang
出处
期刊:PubMed 卷期号:100 (23): 1820-1825
标识
DOI:10.3760/cma.j.cn112137-20190924-02105
摘要

Objective: To investigate the effect of maslinic acid (MA) on isoproterenol (ISO)-induced myocardial fibrosis in mice. Methods: ISO was used to induce myocardial fibrosis in adult male C57BL/6 mice, and MA was administered for two weeks to detect the effects of MA on cardiac function and fibrosis. Molecular changes of fibrosis markers and signaling pathways were detected by RT-PCR and western blotting. Phosphate buffer saline (PBS), PBS+SB203580 (p38 MAPK inhibitor), PBS+MA, ISO, ISO+SB203580, ISO+MA were added to the primary cultured rat fibroblasts. Cells were collected after 48 h for subsequent detection. Results: In this study, the mouse model of myocardial fibrosis was successfully established. The left ventricular faction shortening (FS) and maximum rate of rise and maximum rate of fall of pressure in left ventricular chamber (±dp/dt) of the ISO+MA group were significantly higher than those of the ISO group ((35.1±1.8)% vs (28.5±2.6)%, (7 256±153) mmHg/s vs (6 402±240) mmHg/s, (7 156±163) mmHg/s vs (6 319±219) mmHg/s, all P<0.05). The levels of interstitial and perivascular collagen deposition in the ISO+MA group were higher than those in the ISO group (P<0.05), the relative mRNA levels of COL-1, COL-3 and TGF-β in the ISO+MA group were significantly lower than those in the ISO group, with the relative expression levels of 1.70±0.24 vs 3.69±0.34, 1.72±0.56 vs 4.84±0.82, 1.52±0.19 vs 2.64±0.29, respectively (all P<0.05). The phosphorylation levels of p38 MAPK, Smad3 and protein expression level of TGF-β1 in ISO+MA group were lower than those in ISO group (relative expression levels were 1.67±0.35 vs 2.61±0.58, 1.68±0.23 vs 2.52±0.19,1.56±0.15 vs 2.48±0.26, respectively, all P<0.05). The results of in vitro cell experiments showed that the mRNA levels of COL-1, COL-3 and TGF-β in the SB203580 and MA groups were significantly lower than those in the ISO group (relative expression levels were 2.25±0.51, 2.16±0.48 vs 5.29±1.21; 1.58±0.34, 1.69±0.29 vs 4.97±1.32; 1.41±0.31, 1.55±0.38 vs 3.53±0.56, respectively, all P<0.05). The phosphorylation levels of p38 MAPK and Smad3 in the SB203580 MA groups was significantly lower than those in the ISO group, and the protein expression level of TGF-β1 was lower than that in the ISO group (1.81±0.18, 1.77±0.16 vs 2.56±0.32; 1.85±0.21, 1.81±0.17 vs 2.48±0.37; 1.84±0.24, 1.72±0.17 vs 2.52±0.29, all P<0.05). Conclusion: Maslinic acid can inhibit the phosphorylation of p38 MAPK, thereby preventing the canonical TGF-β1/Smads fibrosis signaling pathway to achieve an anti-fibrosis role.目的: 探讨山楂酸(MA)对异丙肾上腺素(ISO)诱导的小鼠心肌纤维化的影响。 方法: 使用ISO诱导成年雄性C57BL/6小鼠心肌纤维化,MA给药2周,检测MA对心功能和纤维化的影响。RT-PCR和免疫印迹检测纤维化标志物和信号通路分子变化。将原代培养的大鼠成纤维细胞中分别加入磷酸缓冲盐溶液(PBS)、PBS+p38 MAPK抑制剂(SB203580)、PBS+MA、ISO、ISO+SB203580、ISO+MA。48 h后收集细胞进行后续检测。 结果: 本研究成功制备心肌纤维化小鼠模型,ISO+MA组的左心室短轴缩短率(FS)和左心室内压最大上升速率和最大下降速率(±dp/dt)显著高于ISO组[分别为(35.1±1.8)%比(28.5±2.6)%、(7 256±153)mmHg/s比(6 402±240)mmHg/s、(7 156±163)mmHg/s比(6 319±219)mmHg/s,P<0.05];ISO+MA组间质和血管周胶原沉积程度高于ISO组(P<0.05),ISO+MA组的COL-1、COL-3和TGF-β mRNA相对水平显著低于ISO组(1.70±0.24比3.69±0.34、1.72±0.56比4.84±0.82、1.52±0.19比2.64±0.29,P<0.05);ISO+MA组的p38 MAPK和Smad3的磷酸化水平和TGF-β1蛋白表达水平低于ISO组(1.67±0.35比2.61±0.58、1.68±0.23比2.52±0.19、1.56±0.15比2.48±0.26,P<0.05);体外细胞实验结果显示,p38 MAPK特异性抑制剂(SB203580)组和MA组的COL-1、COL-3、TGF-β mRNA水平均显著低于ISO组(分别为2.25±0.51,2.16±0.48比5.29±1.21;1.58±0.34,1.69±0.29比4.97±1.32;1.41±0.31,1.55±0.38比3.53±0.56,P<0.05);SB203580组和MA组的p38 MAPK、Smad3的磷酸化水平均显著低于ISO组,TGF-β1的蛋白表达低于ISO组(分别为1.81±0.18,1.77±0.16比2.56±0.32;1.85±0.21,1.81±0.17比2.48±0.37;1.84±0.24,1.72±0.17比2.52±0.29,P<0.05)。 结论: MA可抑制p38 MAPK的磷酸化,进而抑制经典的TGF-β1/Smads纤维化信号通路来发挥抗纤维化的作用。.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
优美的小丸子完成签到,获得积分20
1秒前
3秒前
乐乐乐发布了新的文献求助10
3秒前
风趣的老太应助chen采纳,获得10
3秒前
3秒前
脑洞疼应助CYY采纳,获得10
3秒前
4秒前
传奇3应助澡雪采纳,获得10
4秒前
5秒前
Dobrzs完成签到,获得积分10
5秒前
6秒前
一只冬瓜zZ完成签到,获得积分10
6秒前
轻松的亦寒应助zcvxd采纳,获得20
6秒前
7秒前
7秒前
fst完成签到,获得积分10
8秒前
ping发布了新的文献求助10
9秒前
土豆淀粉发布了新的文献求助10
9秒前
彼岸花发布了新的文献求助10
11秒前
量子星尘发布了新的文献求助10
11秒前
12秒前
12秒前
LHT完成签到,获得积分10
12秒前
tex发布了新的文献求助10
12秒前
13秒前
乐乐乐完成签到,获得积分10
13秒前
14秒前
共享精神应助博修采纳,获得10
15秒前
内向芒果发布了新的文献求助10
17秒前
SCI发发完成签到,获得积分10
18秒前
李健应助1cf采纳,获得10
19秒前
今后应助tjusasa采纳,获得10
20秒前
筱筱完成签到,获得积分10
20秒前
kk发布了新的文献求助10
20秒前
小月986完成签到,获得积分10
21秒前
22秒前
宋宋发布了新的文献求助10
24秒前
ping完成签到,获得积分10
24秒前
25秒前
昊天锤完成签到,获得积分10
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975816
求助须知:如何正确求助?哪些是违规求助? 3520159
关于积分的说明 11201128
捐赠科研通 3256541
什么是DOI,文献DOI怎么找? 1798347
邀请新用户注册赠送积分活动 877539
科研通“疑难数据库(出版商)”最低求助积分说明 806426