The mechanism of tangerine regulating autophagy and promoting the occurrence and development of abdominal aortic aneurysm in rats based on adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway

Wang Dapeng; Feng Yujing; Zhang Shuo; Ren Qingshuai; Pei Jianjun; Zhao Changquan

doi:10.3760/j.issn.1673-4777.2024.03.007

Abstract：Objective To explore the mechanism of tangerine regulating autophagy and promoting the occurrence and development of abdominal aortic aneurysm(AAA)in rats based on adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Totally 45 female SD rats with specific pathogen-free grade were selected.Of which 20 rats were subcutaneously implanted with 0.9％sodium chloride injection sustained-release pumps(control group),and the remaining 25 rats were subcuta-neously implanted angiotensin Ⅱ sustained-release pumps(AAA group)to build AAA model.During the modeling process,5 rats in the AAA group died,and a total of 20 rats were successfully modeled.The control group was given 0.9％sodium chloride injection intragastric administration and the AAA group was given tangerine intragastric administration once a day for 7 d.The aortic vascular smooth muscle cell viability,cell apoptosis rate,and cell migration rate of rats were observed.The cell protein level,autophagy cell gene expression and cell factor level,and AMPK/mTOR signaling pathway expression of the two groups were compared.Results The cell viability in the AAA group was higher than that in the control group,and the cell apoptosis rate and cell migration rate were lower than those of control group(all P＜0.05).The levels of β-catenin and B cell lymphoma 2(Bcl-2)associated X protein were lower than those in the control group,and the levels of cyclin D1 and Bcl-2 were higher than those in the control group(all P＜0.05).The gene expressions of Beclin1,Atg4b,Bnip3,Vps34 and LC3 were lower than those in the control group(all P=0.001).The levels of interleukin-6,cytokines expressed and secreted by normal T lymphocytes,transform growth factors-β,insulin-like growth factor-1 and monocytes chemotactic proteins-1 were lower than those in the control group(all P＜0.05),and the expressions of AMPK and mTOR were higher than those in the control group[(1.61±0.35)vs(1.10±0.21),(2.11±0.14)vs(1.13± 0.06)](both P=0.001).Conclusions Tangeretin has an ameliorative effect on the levels of cell protein level,autophagy level and transforming growth factor level inAAA rats,and its mechanism may be associated with the regulation of AMPK/mTOR signaling pathways.