The repressing effect of fenoldopam on the development of thoracic aortic aneurysm in mice
10.19405/j.cnki.issn1000-1492.2024.04.002
- Author:
Ying Zhou
1
,
2
;
Lifei Wu
1
,
2
,
3
;
Wenjing Du
4
;
Jimin Cao
1
,
2
Author Information
1. Key Laboratory of Cellular Physiology at Shanxi Medical University , Ministry of Education , Taiyuan 030000
2. Dept of Physiology ,Shanxi Medical University , Taiyuan 030000
3. Dept of Pathophysiology , Shanxi Medical University , Taiyuan 030000
4. State Key Laboratory of Medical Molecular Biology , Dept of Cell Biology , Institute of Basic Medical Sciences Chinese Academy of Medical Sciences , School of Basic Medicine Peking Union Medical College , Beijing 100000
- Publication Type:Journal Article
- Keywords:
thoracic aortic aneurysm;
dopamine receptors;
fenoldopam;
macrophages;
inflammation;
extracellu- lar matrix degradation
- From:
Acta Universitatis Medicinalis Anhui
2024;59(4):569-575
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate whether fenoldopam (FNDP) ( an agonist of type 1 dopamine receptor) has a protective effect on thoracic aortic aneurysm ( TAA) in mice .
Methods :Three-week-old male C57BL/6J mice were treated with β-aminopropionitrile (BAPN) to induce TAA . The mice were divided into three groups : the con- trol group , the BAPN group , and the BAPN + FNDP group (FNDP inj ected intraperitoneally) . The incidence and survival rate of TAA were recorded . Gross anatomy of the whole aortae was ob served . Elastin staining was per- formed to assess morphological change , while immunohistochemistry was employed to evaluate the expressions of matrix metalloproteinase 2(MMP2) , matrix metalloproteinase 9( MMP9) and cluster of differentiation 68( CD68) respectively. Gelatin zymography was conducted to assess MMP2 and MMP9 activity. Reverse transcription-poly- merase chain reaction (RT-PCR) was performed to measure the mRNA expression levels of dopamine receptor D1(D1DR) , dopamine receptor d2 (D2DR) , dopamine receptor d3 (D3DR) , dopamine receptor d5 (D5DR) , in- terleukin-1β(IL-1β) , interleukin-6 (IL-6) , tumour necrosis factor-α (TNF-α) , monocyte chemoattractant pro- tein-1 (MCP-1) , alpha-smooth muscle actin ( α-SMA) and smooth muscle protein 22 -alpha (SM22α) .
Results:Compared to the control group , the BAPN group exhibited significant formation of TAA . Elastic fiber disruption was also ob served in the thoracic aortic wall , along with a significant decrease in the mRNA levels of D1DR and D5DR. The BAPN + FNDP group showed a significant reduction in the incidence of TAA formation and the rate of aneu- rysm rupture compared to the BAPN group . The disruption and rupture of elastic fibers in the thoracic aortic wall were significantly improved in the BAPN + FNDP group . The levels of MMP2 and MMP9 in the thoracic aortic wall significantly decreased , and the enzymatic activity of MMP2 in the serum was significantly reduced . Moreover , macrophage infiltration in the thoracic aortic wall was significantly reduced and the mRNA levels of IL-1β, IL-6 , TNF-αand MCP-1 also significantly decreased after FNDP treatment. There was no statistically significant differ- ence in the mRNA levels of α-SMA and SM22α.
Conclusion :FNDP shows an inhibitory effect on TAA progres- sion in mice , suggesting a potential of FNDP as a therapeutic agent for TAA .
- Full text:2024062809150091711非诺多泮抑制小鼠胸主动脉瘤的实验研究_周莹.pdf
