北京中医药大学学报2024，Vol.47Issue(11)：1550-1561,12.DOI:10.3969/j.issn.1006-2157.2024.11.010
三七总皂苷抑制JNK/c-Jun信号通路干预钙化性主动脉瓣疾病的效应及机制研究
The effect and mechanism of Panax notoginseng saponins through inhibiting JNK/c-Jun signaling pathway in calcific aortic valve disease
摘要
Abstract
Objective To investigate the effect and mechanism of Panax notoginseng saponins(PNS)in inhibiting c-Jun N-terminal protein kinase(JNK)/c-Jun signaling pathway activation to alleviate calcific aortic valve disease(CAVD)in mice.Methods Twenty-one male ApoE-/-mice aged 6 to 8 weeks were randomly divided into the model,PNS high-dose(60 mg/kg),and PNS low-dose(30 mg/kg)groups using the random number table method,with seven mice per group.Nine male C57BL/6 mice aged 6 to 8 weeks were used as the control group.Mice in the control group were fed a normal diet,whereas ApoE-/-mice were fed a high-fat diet for 12 weeks.After 12 weeks,three C57BL/6 and three ApoE-/-mice(one ApoE-/-mice from each group)were randomly selected to evaluate the CAVD modeling effect.After confirming successful modeling,the PNS high-and low-dose groups received daily intragastric PNS administration.The control and model groups were administered an equal volume of stroke-physiological saline solution by gavage for 4 consecutive weeks.The valve annulus diameter and peak velocity of the mice in each group were then detected using ultrasound.The degree of aortic valve calcification was evaluated using von Kossa and Alizarin Red S staining.The serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Inflammatory factor interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)levels were determined using an enzyme-linked immunosorbent assay.The expressions of calcification markers,runt-related transcription factor 2(RUNX2),and bone morphogenetic protein 2(BMP2)were detected using immunohistochemistry.Aortic valve cell apoptosis was evaluated using TUNEL staining,and JNK/c-Jun signaling pathway-related mRNA and mean fluorescence intensity were detected using quantitative real-time PCR and immunofluorescence,respectively.Results Compared with the control group,the mice in the model group showed an increase in serum TC,TG,LDL-C,TNF-α,and IL-1β levels,a decrease in IL-4 and IL-10 levels,a decrease in annulus diameter,an increase in peak flow velocity,and an increase in von Kossa and Alizarin Red S staining-positive areas.Additionally,the model group showed an increase in aortic valve cell apoptosis rate,an increase in BMP2 and RUNX2-positive rates,and an increase in JNK and c-Jun mRNA expression levels and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Compared to the model group,the PNS low-dose group showed a decrease in serum TC,LDL-C,and TNF-α levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in positive area in Alizarin Red S staining.Furthermore,the PNS low-dose group showed a decrease in BMP2 and RUNX2-positive rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).The PNS high-dose group showed an increase in HDL-C,IL-4 and IL-10 levels,a decrease in serum TC,LDL-C,TNF-α,and IL-1β levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in von Kossa and Alizarin Red S staining-positive areas and cell apoptosis rate.The PNS high-dose group also showed a decrease in BMP2 and RUNX2 positive staining rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Conclusion PNS may reduce valvular cell apoptosis,alleviate inflammation,and protect against aortic valve calcification in mice by inhibiting the activation of JNK/c-Jun signaling pathway.关键词
三七总皂苷/细胞凋亡/c-Jun氨基端激酶/c-Jun信号通路/主动脉瓣/钙化性主动脉瓣疾病/小鼠Key words
Panax notoginseng saponins/apoptosis/c-Jun N-terminal protein kinase/c-Jun signaling pathway/aortic valve/calcific aortic valve disease/mice分类
医药卫生引用本文复制引用
李洪峥,陈可冀,刘天娇,商祖诚,栗梦凡,林国晟,张斌,于子凯,付长庚,吴永健..三七总皂苷抑制JNK/c-Jun信号通路干预钙化性主动脉瓣疾病的效应及机制研究[J].北京中医药大学学报,2024,47(11):1550-1561,12.基金项目
国家自然科学基金青年基金项目(No.82104679) （No.82104679）
中国中医科学院基本科研业务费优秀青年科技人才培养专项(No.ZZ15-YQ-004) （No.ZZ15-YQ-004）
中国中医科学院西苑医院能力提升项目(No.XYZX0101-37,No.YJMPSC202422) National Natural Science Foundation of China(No.82104679) （No.XYZX0101-37,No.YJMPSC202422）
