Establishment of a rat model with aortic dissection induced by β-aminopropionitrile combined with angiotensin <b>Ⅱ</b>_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Yi ¹ , LIU Xinmei ² , ZHOU Guangqi ³ , QIAO Yanli ⁴ , HU Haiyang ¹ ,  LIU Hongsheng ²

1. Clinical Medical College of Jining Medical University, Jining, 272013, Shandong, P. R. China;
2. Department of Cardiac Intensive Medicine, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, P. R. China;
3. Department of Breast Surgery, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, P. R. China;
4. Department of Cardiac Surgery, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, P. R. China;

Corresponding author：

LIU Hongsheng, Email: 18678766889@163.com

Keywords：

β-aminopropionitrile; angiotensin Ⅱ; aortic dissection; rat; model; complications

DOI：

10.7507/1007-4848.202203068

Video：

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Objective To investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. Methods Forty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. Results There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. Conclusion The combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.

Citation： ZHANG Yi, LIU Xinmei, ZHOU Guangqi, QIAO Yanli, HU Haiyang, LIU Hongsheng. Establishment of a rat model with aortic dissection induced by β-aminopropionitrile combined with angiotensin Ⅱ. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(1): 127-134. doi: 10.7507/1007-4848.202203068 Copy

1.	Erbel R, Aboyans V, Boileau C, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J, 2014, 35(41): 2873-2926.
2.	Gawinecka J, Schönrath F, von Eckardstein A. Acute aortic dissection: Pathogenesis, risk factors and diagnosis. Swiss Med Wkly, 2017, 147: w14489.
3.	Bielajew BJ, Hu JC, Athanasiou KA. Collagen: Quantification, biomechanics, and role of minor subtypes in cartilage. Nat Rev Mater, 2020, 5(10): 730-747.
4.	Berman AG, Romary DJ, Kerr KE, et al. Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition. Sci Rep, 2022, 12(1): 99.
5.	Zhou H, Ren Y, Xiao J, et al. Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection. Ann Transl Med, 2021, 9(20): 1574.
6.	Montezano AC, Nguyen Dinh Cat A, Rios FJ, et al. Angiotensin Ⅱ and vascular injury. Curr Hypertens Rep, 2014, 16(6): 431.
7.	Ames MK, Atkins CE, Pitt B. The renin-angiotensin-aldosterone system and its suppression. J Vet Intern Med, 2019, 33(2): 363-382.
8.	Zhang Y, Lin X, Chu Y, et al. Dapagliflozin: A sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin Ⅱ-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling. Cardiovasc Diabetol, 2021, 20(1): 121.
9.	Liu C, Zhang C, Jia L, et al. Interleukin-3 stimulates matrix metalloproteinase 12 production from macrophages promoting thoracic aortic aneurysm/dissection. Clin Sci (Lond), 2018, 132(6): 655-668.
10.	Ren W, Liu Y, Wang X, et al. β-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL/6 mice. Sci Rep, 2016, 6: 28149.
11.	Jia LX, Zhang WM, Zhang HJ, et al. Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection. J Pathol, 2015, 236(3): 373-383.
12.	王杨, 龚德军, 袁扬, 等. 主动脉夹层小鼠血管壁中微管相关蛋白1轻链3、Beclin1及骨桥蛋白的表达及意义. 中华胸心血管外科杂志, 2014, 30(12): 753-757.
13.	Chen T, Jiang N, Zhang S, et al. BAPN-induced rodent model of aortic dissecting aneurysm and related complications. J Thorac Dis, 2021, 13(6): 3643-3651.
14.	高艳香, 刘瑜婷, 张亚运, 等. β-氨基丙腈饮水建立小鼠主动脉夹层模型. 中华心血管病杂志, 2018, 46(2): 137-142.
15.	吴锡阶, 卢琳, 陈良万, 等. 联合应用β-氨基丙腈和血管紧张素Ⅱ建立SD大鼠主动脉夹层模型. 中华胸心血管外科杂志, 2018, 34(11): 664-667.
16.	张雷, 王亮, 陆华, 等. 主动脉夹层大鼠模型及其力学机制的研究. 中华外科杂志, 2012, 50(12): 1108-1112.
17.	Izawa-Ishizawa Y, Imanishi M, Zamami Y, et al. Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses. J Hypertens, 2019, 37(1): 73-83.
18.	Kurihara T, Shimizu-Hirota R, Shimoda M, et al. Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection. Circulation, 2012, 126(25): 3070-3080.
19.	Xing C, Jiang D, Liu Y, et al. Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis. Genes Dis, 2022, 9(1): 140-150.
20.	Miana M, Galán M, Martínez-Martínez E, et al. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats. Dis Model Mech, 2015, 8(6): 543-551.
21.	Siri S, Maier F, Chen L, et al. Differential biomechanical properties of mouse distal colon and rectum innervated by the splanchnic and pelvic afferents. Am J Physiol Gastrointest Liver Physiol, 2019, 316(4): G473-G481.
22.	Maier F, Siri S, Santos S, et al. The heterogeneous morphology of networked collagen in distal colon and rectum of mice quantified via nonlinear microscopy. J Mech Behav Biomed Mater, 2021, 113: 104116.
23.	柯敏辉, 李雪玉, 许振国. 直肠黏膜内脱垂组织中胶原纤维变化和CD68、BFGF、VEGF的表达及意义. 山西医科大学学报, 2022, 53(2): 227-231.
24.	Hayashi K, Fong KS, Mercier F, et al. Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: Changes in the expression of LOXL during development and growth of mouse tissues. J Mol Histol, 2004, 35(8-9): 845-855.

1. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J, 2014, 35(41): 2873-2926.
2. Gawinecka J, Schönrath F, von Eckardstein A. Acute aortic dissection: Pathogenesis, risk factors and diagnosis. Swiss Med Wkly, 2017, 147: w14489.
3. Bielajew BJ, Hu JC, Athanasiou KA. Collagen: Quantification, biomechanics, and role of minor subtypes in cartilage. Nat Rev Mater, 2020, 5(10): 730-747.
4. Berman AG, Romary DJ, Kerr KE, et al. Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition. Sci Rep, 2022, 12(1): 99.
5. Zhou H, Ren Y, Xiao J, et al. Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection. Ann Transl Med, 2021, 9(20): 1574.
6. Montezano AC, Nguyen Dinh Cat A, Rios FJ, et al. Angiotensin Ⅱ and vascular injury. Curr Hypertens Rep, 2014, 16(6): 431.
7. Ames MK, Atkins CE, Pitt B. The renin-angiotensin-aldosterone system and its suppression. J Vet Intern Med, 2019, 33(2): 363-382.
8. Zhang Y, Lin X, Chu Y, et al. Dapagliflozin: A sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin Ⅱ-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling. Cardiovasc Diabetol, 2021, 20(1): 121.
9. Liu C, Zhang C, Jia L, et al. Interleukin-3 stimulates matrix metalloproteinase 12 production from macrophages promoting thoracic aortic aneurysm/dissection. Clin Sci (Lond), 2018, 132(6): 655-668.
10. Ren W, Liu Y, Wang X, et al. β-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL/6 mice. Sci Rep, 2016, 6: 28149.
11. Jia LX, Zhang WM, Zhang HJ, et al. Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection. J Pathol, 2015, 236(3): 373-383.
12. 王杨, 龚德军, 袁扬, 等. 主动脉夹层小鼠血管壁中微管相关蛋白1轻链3、Beclin1及骨桥蛋白的表达及意义. 中华胸心血管外科杂志, 2014, 30(12): 753-757.
13. Chen T, Jiang N, Zhang S, et al. BAPN-induced rodent model of aortic dissecting aneurysm and related complications. J Thorac Dis, 2021, 13(6): 3643-3651.
14. 高艳香, 刘瑜婷, 张亚运, 等. β-氨基丙腈饮水建立小鼠主动脉夹层模型. 中华心血管病杂志, 2018, 46(2): 137-142.
15. 吴锡阶, 卢琳, 陈良万, 等. 联合应用β-氨基丙腈和血管紧张素Ⅱ建立SD大鼠主动脉夹层模型. 中华胸心血管外科杂志, 2018, 34(11): 664-667.
16. 张雷, 王亮, 陆华, 等. 主动脉夹层大鼠模型及其力学机制的研究. 中华外科杂志, 2012, 50(12): 1108-1112.
17. Izawa-Ishizawa Y, Imanishi M, Zamami Y, et al. Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses. J Hypertens, 2019, 37(1): 73-83.
18. Kurihara T, Shimizu-Hirota R, Shimoda M, et al. Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection. Circulation, 2012, 126(25): 3070-3080.
19. Xing C, Jiang D, Liu Y, et al. Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis. Genes Dis, 2022, 9(1): 140-150.
20. Miana M, Galán M, Martínez-Martínez E, et al. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats. Dis Model Mech, 2015, 8(6): 543-551.
21. Siri S, Maier F, Chen L, et al. Differential biomechanical properties of mouse distal colon and rectum innervated by the splanchnic and pelvic afferents. Am J Physiol Gastrointest Liver Physiol, 2019, 316(4): G473-G481.
22. Maier F, Siri S, Santos S, et al. The heterogeneous morphology of networked collagen in distal colon and rectum of mice quantified via nonlinear microscopy. J Mech Behav Biomed Mater, 2021, 113: 104116.
23. 柯敏辉, 李雪玉, 许振国. 直肠黏膜内脱垂组织中胶原纤维变化和CD68、BFGF、VEGF的表达及意义. 山西医科大学学报, 2022, 53(2): 227-231.
24. Hayashi K, Fong KS, Mercier F, et al. Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: Changes in the expression of LOXL during development and growth of mouse tissues. J Mol Histol, 2004, 35(8-9): 845-855.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Establishment of a rat model with aortic dissection induced by β-aminopropionitrile combined with angiotensin Ⅱ

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