海南医科大学学报2026,Vol.32Issue(10):739-750,12.DOI:10.13210/j.cnki.jhmu.20250528.002
益肺宣肺降浊方调节STAT5/RIPK3/MLKL通路干预VaD坏死性凋亡的实验研究
Mechanistic study of Yifei Xuanfei Jiangzhuo Formula in modulating the STAT5/RIPK3/MLKL pathway to intervene in VaD-Related necroptosis
摘要
Abstract
Objective:To investigate the effect and mechanism of Yifei Xuanfei Jiangzhuo Formula on necrotic apoptosis in vascular dementia(VaD)model rats,this study takes the STAT5/RIPK3/MLKL pathway as the starting point.Methods:In this study,50 male SD rats were selected,of which 40 were established using the bilateral common carotid artery permanent ligation(2-VO)method.They were randomly divided into a model group,a low-dose group of YifeiXuanfeiJiangzhuo Formula,a high-dose group,and a donepezil hydrochloride group.Additionally,10 SHAM group rats were also included.Using Morris water maze test to evaluate the learning and memory behavior of rats;H&E staining and Nissl staining were used to analyze the patholog-ical morphology of rat hippocampal tissue;Immunofluorescence staining was used to observe the positive expression of STAT5 and p-RIPK3 in the hippocampal tissues of rats in each group;ELISA method was used to detect the levels of IL-10 and TNF-α factors in the serum of rats in each group;Real time PCR was used to detect the mRNA levels of S T A T 5,F A D D,iNOS,and HO-1;Western blot was used to detect the expression of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD proteins in hippocampal tissue.Results:Compared to the SHAM group,the hippocampal tissue of the model group rats showed significant pathological changes,with significantly prolonged escape latency(P<0.05)and significantly reduced platform crossing times(P<0.05),indicating impaired spatial learning and memory function.The level of TNF-α in rat serum increased while the level of IL-10 decreased;The positive expression levels of STAT5 and p-RIPK3 increased in hippocampal tissue;The mRNA expression of S T A T 5,F A D D,iNOS,and HO-1 increased in hippocampal tissue.The protein expression levels of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD also increased in hippocampal tissue.Compared to the model group,the YifeiXuanfeiJi-angzhuo Formula significantly reduced hippocampal tissue damage and improved learning and memory abilities in VaD rats.It regu-lated the levels of IL-10 and TNF-α factors in serum,reduced the mRNA levels of STAT5,FADD,iNOS,and HO-1,as well as the positive expression levels of STAT5 and p-RIPK3 in hippocampal tissue,and inhibited the protein expression of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD(P<0.05).Conclusion:YifeiXuanfeiJiangzhuo Formula alleviates the pathologi-cal manifestations and inflammatory response of VaD rats by inhibiting the necrotic apoptosis pathway,thereby improving their memory and learning abilities.关键词
血管性痴呆/益肺宣肺降浊方/STAT5/RIPK3/MLKL通路/坏死性凋亡Key words
Vascular dementia/Yifei Xuanfei Jiangzhuo Formula/STAT5/RIPK3/MLKL pathway/Necroptosis分类
医药卫生引用本文复制引用
符钰岚,陈炜,卓桂锋,朱小敏,黄颖睿,张颖,顾洋,曹薛源,吴林..益肺宣肺降浊方调节STAT5/RIPK3/MLKL通路干预VaD坏死性凋亡的实验研究[J].海南医科大学学报,2026,32(10):739-750,12.基金项目
This study was supported by the National Natural Science Foundation of China(82374387 ()
82160885) ()
Guangxi Natural Science Foundation(2024JJA141356) (2024JJA141356)
Key Discipline Construction Project of Traditional Chinese Medicine in Guangxi(GZXK-Z-20-13) (GZXK-Z-20-13)
Guangxi University of Traditional Chinese Medicine's"Qihuang Project"High level Talent Cultivation Project(202410) 国家自然科学基金(82374387 (202410)
82160885) ()
广西自然科学基金(2024JJA141356) (2024JJA141356)
广西中医药重点学科建设项目(GZXK-Z-20-13) (GZXK-Z-20-13)
广西中医药大学"岐黄工程"高层次人才培育项目(202410). (202410)