中国药房2023，Vol.34Issue(24)：2987-2994,8.DOI:10.6039/j.issn.1001-0408.2023.24.06
飞龙掌血对胶原诱发关节炎大鼠心血管损害的干预作用及机制
Intervention effects and mechanism of Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis
摘要
Abstract
OBJECTIVE To investigate the intervention effects and potential mechanism of Miao medicine Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis(CIA)based on vitamin D(VD)and neutrophil extracellular traps(NETs).METHODS SD rats were randomly divided into the normal group(9 rats)and the modeling group(61 rats).CIA model was prepared by multi-point injection of type Ⅱ bovine collagen+Fisher's incomplete adjuvant;the model rats were randomly divided into the model group,methotrexate group(positive control,1.5 mg/kg,twice a week),vitamin D group[pathway validation,1 000 IU/(kg·d),once a day],T.asiatica low-dose,medium-dose and high-dose groups[0.54,1.08,2.16 g/(kg·d),calculated by crude drug,once a day],with 9 rats in each group;they were given relevant medicine intragastrically for 4 consecutive weeks.Arthritis index scoring was performed after modeling and before administration,and plantar thickness was measured before and after the last administration;the histopathological changes of ankle joint,heart and abdominal aorta were observed in rats;the serum contents of myeloperoxidase(MPO),interleukin-6(IL-6)and 25-hydroxyvitamin D3[25(OH)D3]were detected;the expressions of peptidylarginine deiminase 4(PAD4),NETs markers[citrullinated histone H3(CitH3),MPO],VD-related indicators[vitamin D receptor(VDR),25-hydroxyvitamin D-1α-hydroxylase(CYP27B1)]and IL-6 were determined in cardiac tissue.RESULTS Compared with the normal group,the plantar thickness of the arthritis index increased significantly in the model group(P＜0.01).The obvious inflammatory cell infiltration and fibrous tissue hyperplasia were found in the ankle joint,the obvious myocardial fiber vacuoles and thickening of some surrounding blood vessel walls were found in the heart tissue,and the endothelial detachment was found in the abdominal aorta.The contents of MPO and IL-6 in serum increased significantly(P＜0.01),while the level of 25(OH)D3 decreased significantly(P＜0.01);the protein expressions of PAD4,CitH3,MPO and IL-6 in myocardial tissue up-regulated significantly(P＜0.01),while protein expression of VDR and CYP27B1 changed to acertain extent without significance(P＞0.05).Compared with the model group,the pathological changes of ankle joints and cardiac tissue in rats were significantly improved in administration groups,and the above indicators were generally reversed(P＜0.05 or P＜0.01).CONCLUSIONS T.asiatica can improve rheumatoid arthritis symptoms and cardiovascular damage by inhibiting the formation of NETs and inflammatory response,the mechanism of which may be associated with the regulation of VD expression.关键词
飞龙掌血/类风湿性关节炎/心血管损害/中性粒细胞胞外诱捕网/维生素DKey words
Toddalia asiatica/rheumatoid arthritis/cardiovascular damage/neutrophil extracellular trapping net/vitamin D分类
医药卫生引用本文复制引用
李月兴,陈波洋,李倩,陈帅,陈云志..飞龙掌血对胶原诱发关节炎大鼠心血管损害的干预作用及机制[J].中国药房,2023,34(24):2987-2994,8.基金项目
国家自然科学基金项目(No.82260890) （No.82260890）
2021年国家自然科学基金后补助资金科研创新探索专项(No.2019YFC1712504-04) （No.2019YFC1712504-04）
贵州省教育厅滚动支持省属高校科研平台团队项目(No.黔教技[2022]023号) （No.黔教技[2022]023号）
贵州中医药大学2021年度科研创新和探索专项(No.2019YFC171250101) （No.2019YFC171250101）
