The repressing effect of fenoldopam on the development of thoracic aortic aneurysm in mice
10.19405/j.cnki.issn1000-1492.2024.04.002
- VernacularTitle:非诺多泮抑制小鼠胸主动脉瘤的实验研究
- Author:
Ying ZHOU
1
,
2
;
Lifei WU
;
Wenjing DU
;
Jimin CAO
Author Information
1. 山西医科大学细胞生理学教育部重点实验室,太原 030000
2. 山西医科大学生理学系,太原 030000
- 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 injected intraperitoneally).The incidence and survival rate of TAA were recorded.Gross anatomy of the whole aortae was observed.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 observed 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-α and 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
