CAI Qiang,LIU Liuqing,TANG Jiayu.Effects of astragaloside Ⅳ on arterial endothelial tissue damage in rats with intracranial aneurysm[J].ZHONGGUO YAOFANG,2025,36(13):1617-1621.
CAI Qiang,LIU Liuqing,TANG Jiayu.Effects of astragaloside Ⅳ on arterial endothelial tissue damage in rats with intracranial aneurysm[J].ZHONGGUO YAOFANG,2025,36(13):1617-1621. DOI: 10.6039/j.issn.1001-0408.2025.13.11.
Effects of astragaloside Ⅳ on arterial endothelial tissue damage in rats with intracranial aneurysm
To investigate the effect of astragaloside Ⅳ(AST) on the injury of arterial endothelial tissue in rats with intracranial aneurysms (IA), and to explore its mechanism of action based on the nuclear factor κB (NF-κB)/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) signaling pathway.
METHODS
2
Rats were divided into Sham group (intragastric administration and intraperitoneal injection of the same volume of normal saline), IA group (intragastric administration and intraperitoneal injection of the same volume of normal saline), AST low-dose group (AST-L group, intragastric administration of 40 mg/kg AST), AST high-dose group (AST-H group, intragastric administration of 80 mg/kg AST), AST-H+HY-N2485 group [intragastric administration of 80 mg/kg AST and intraperitoneal injection of 25 mg/kg HY-N2485 (activator of NF-κB/NLRP3 signaling pathway)]. They were given relevant medicine, once a day, for 8 consecutive weeks. After last medication, the levels of inflammatory factors [serum tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), IL-6] and vascular endothelial growth factor (VEGF) and endothelin (ET) were detected; the morphology of IA was observed; the expressions of von Willebrand factor (vWF), vascular cell adhesion molecule-1 (VCAM-1), endothelial nitric oxide synthase (eNOS), and NF-κB/NLRP3 pathway related proteins in vascular tissue were also determined.
RESULTS
2
Compared with the Sham group, the basilar arterial ring of rats in the IA group had obvious protrusions, and the arterial vascular endothelial cells were significantly damaged. The levels of inflammatory factors, VEGF and ET in serum, as well as the expression levels of vWF, VCAM-1 and NLRP3 proteins and the phosphorylation level of NF-κB protein in vascular tissues were increased significantly (
P
<0.05). Aneurysms and ruptures of the internal elastic layer were significantly increased (
P
<0.05), while the expression level of eNOS protein was significantly decreased (
P
<0.05). Compared with IA group, the morphology of IA and the levels of above indexes were all improved signi
ficantly in AST-L and AST-H groups (
P
<0.05),and the improvement in the AST-H group was more significant than that in the AST-L group (
P
<0.05); HY-N2485 could attenuate the improvement effect of AST on vascular endothelial tissue damage in IA rats (
P
<0.05).
CONCLUSIONS
2
AST may inhibit the expression of inflammatory factors, alleviate inflammation and vascular endothelial tissue damage in IA rats by inhibiting NF-κB/NLRP3 signaling pathway, thereby inhibiting the formation of IA.
关键词
Keywords
references
NAFEES AHMED S , PRAKASAM P . A systematic review on intracranial aneurysm and hemorrhage detection using machine learning and deep learning techniques [J ] . Prog Biophys Mol Biol , 2023 , 183 : 1 - 16 .
STRANGE F , GRUTER B E , FANDINO J , et al . Preclinical intracranial aneurysm models:a systematic review [J ] . Brain Sci , 2020 , 10 ( 3 ): 134 .
HUANG J X , ZHANG H , YOU L T , et al . Coenzyme Q10 inhibits intracranial aneurysm formation and progression in a mouse model [J ] . Pediatr Res , 2022 , 91 ( 4 ): 839 - 845 .
ZHAO Y L , SHAO C Y , ZHOU H F , et al . Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway [J ] . Phytomedicine , 2023 , 119 : 155002 .
YU X J , WANG Y G , LU R , et al . BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity [J ] . Mol Med , 2023 , 29 ( 1 ): 30 .
SUN B , LIU Z H , YU Z Q . miRNA-323a-3p promoted intracranial,aneurysm-induced inflammation via AMPK/NF-κB signaling pathway by AdipoR1 [J ] . Adv Clin Exp Med , 2022 , 31 ( 11 ): 1243 - 1254 .
YANG S Z , LIU Q Y , YANG J H , et al . Increased levels of serum IL-15 and TNF-β indicate the progression of human intracranial aneurysm [J ] . Front Aging Neurosci , 2022 , 14 : 903619 .
SUN J W , ZHANG L F , CHENG Q J , et al . Aberrant expression and regulatory role of histone deacetylase 9 in vascular endothelial cell injury in intracranial aneurysm [J ] . Biomol Biomed , 2024 , 24 ( 1 ): 61 - 72 .
LIU Y , SU Y X , CHEN L , et al . Exploring the roles and therapeutic implications of melatonin-mediated KLF6 in the development of intracranial aneurysm [J ] . Ann Med , 2024 , 56 ( 1 ): 2397568 .
USATEGUI-MARTÍN R , JIMÉNEZ-ARRIBAS P , SAKAS-GANDULLO C , et al . Endothelial nitric oxide synthase rs1799983 gene polymorphism is associated with the risk of developing intracranial aneurysm [J ] . Acta Neurochir (Wien) , 2023 , 165 ( 5 ): 1261 - 1267 .
SU H , LIU B , CHEN H M , et al . LncRNA ANRIL me- diates endothelial dysfunction through BDNF downregulation in chronic kidney disease [J ] . Cell Death Dis , 2022 , 13 ( 7 ): 661 .
ZHANG P Y , WU P F , KHAN U Z , et al . Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway [J ] . J Nanobiotechnology , 2023 , 21 ( 1 ): 332 .
YU H M , LIU Q Y , XIE M H , et al . Nesfatin-1 inhibits cerebral aneurysms by activating Nrf2 and inhibiting NF-κB signaling [J ] . CNS Neurosci Ther , 2024 , 30 ( 8 ): e14864 .
JIANG Z X , HUANG J X , YOU L T , et al . Pharmacological inhibition of STAT3 by BP-1-102 inhibits intracranial aneurysm formation and rupture in mice through modula- ting inflammatory response [J ] . Pharmacol Res Perspect , 2021 , 9 ( 1 ): e00704 .