浏览全部资源
扫码关注微信
贵州中医药大学基础医学院,贵阳 550025
硕士研究生。研究方向:中医证候与物质基础。 E-mail:1908515040@qq.com
教授,博士生导师,博士。研究方向:中医证候与物质基础。E-mail:chenyunzhi270@gzy.edu.cn
纸质出版日期:2023-12-30,
收稿日期:2023-05-16,
修回日期:2023-09-15,
扫 描 看 全 文
李月兴,陈波洋,李倩等.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 Δ[J].中国药房,2023,34(24):2987-2994.
LI Yuexing,CHEN Boyang,LI Qian,et al.Intervention effects and mechanism of Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis[J].ZHONGGUO YAOFANG,2023,34(24):2987-2994.
李月兴,陈波洋,李倩等.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 Δ[J].中国药房,2023,34(24):2987-2994. DOI: 10.6039/j.issn.1001-0408.2023.24.06.
LI Yuexing,CHEN Boyang,LI Qian,et al.Intervention effects and mechanism of Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis[J].ZHONGGUO YAOFANG,2023,34(24):2987-2994. DOI: 10.6039/j.issn.1001-0408.2023.24.06.
目的
2
基于维生素D(VD)和中性粒细胞胞外诱捕网(NETs)探讨苗药飞龙掌血对胶原诱发关节炎(CIA)大鼠心血管损害的干预作用及潜在机制。
方法
2
将SD大鼠随机分为正常组(9只)和造模组(61只)。造模组大鼠以多点注射牛Ⅱ型胶原+弗氏不完全佐剂的方式制备CIA模型。将造模成功的大鼠分为模型组、甲氨蝶呤组(阳性对照,1.5 mg/kg,每周2次)、VD组[通路验证,1 000单位/(kg·d),每天1次]和飞龙掌血低、中、高剂量组[0.54、1.08、2.16 g/(kg·d),以生药量计,每天1次]
,每组9只,灌胃给药4周。于造模后、给药前进行关节炎指数评分,分别于给药前和末次给药后测量足跖厚度,观察大鼠踝关节、心脏和腹主动脉组织病理学变化;检测血清中髓过氧化物酶(MPO)、白细胞介素6(IL-6)、25-羟基维生素D
3
[25(OH)D
3
]含量;检测心脏组织中肽酰基精氨酸脱亚氨酶4(PAD4)、NETs标志物[瓜氨酸化组蛋白H3(CitH3)、MPO]
、VD相关指标[维生素D受体(VDR)、25羟基维生素D-1α羟化酶(CYP27B1)]、IL-6蛋白的表达情况。
结果
2
与正常组比较,模型组大鼠关节炎指数和足跖厚度均显著增加(
P
<0.01),踝关节组织可见明显的炎症细胞浸润和纤维组织增生,心脏组织可见明显的组织空泡和部分周围血管壁增厚,腹主动脉组织可见内皮脱落;血清MPO、IL-6含量显著增高(
P
<0.01),25(OH)D
3
水平显著下降(
P
<0.01);心肌组织中PAD4、CitH3、MPO、IL-6蛋白的表达均显著上调(
P
<0.01);VDR、CYP27B1蛋白的表达虽有改变,但差异均无统计学意义(
P
>0.05)。与模型组比较,各药物组大鼠踝关节、心脏组织的病理改变均明显改善,上述各指标均普遍逆转(
P
<0.05或
P
<0.01)。
结论
2
飞龙掌血可通过抑制NETs的形成及炎症反应的发生来改善类风湿性关节炎症状及相关心血管损害,其机制可能与调节VD水平有关。
OBJECTIVE
2
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
2
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 D
3
[25(OH)D
3
] 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
2
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)D
3
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
2
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.
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D
rheumatoid arthritiscardiovascular damageneutrophil extracellular trapping netvitamin D
RADU A F,BUNGAU S G. Management of rheumatoid arthritis:an overview[J]. Cells,2021,10(11):2857.
GOUZE H,AEGERTER P,SAID-NAHAL R,et al. Rheumatoid arthritis,as a clinical disease,but not rheumatoid arthritis-associated autoimmunity,is linked to cardio-vascular events[J]. Arthritis Res Ther,2022,24(1):56.
MUTUA V,GERSHWIN L J. A review of neutrophil extracellular traps(NETs)in disease:potential anti-NETs therapeutics[J]. Clin Rev Allergy Immunol,2021,61(2):194-211.
ABBAS M A. Physiological functions of vitamin D in adipose tissue[J]. J Steroid Biochem Mol Biol,2017,165(Pt B):369-381.
AO T,KIKUTA J,ISHII M. The effects of vitamin D on immune system and inflammatory diseases[J]. Biomo-lecules,2021,11(11):1624.
ASLAM M M,JOHN P,BHATTI A,et al. Vitamin D as a principal factor in mediating rheumatoid arthritis-derived immune response[J]. Biomed Res Int,2019,2019:3494937.
CHEN C E,WENG H C,ZHANG X X,et al. Low-dose vitamin D protects hyperoxia-induced bronchopulmonary dysplasia by inhibiting neutrophil extracellular traps[J]. Front Pediatr,2020,8:335.
周威,曾庆芳,罗才荣,等. 基于LC-Q-TOF的飞龙掌血根皮极性部位化学成分分析[J]. 中华中医药杂志,2019,34(12):5914-5919.
ZHOU W,ZENG Q F,LUO C R,et al. Analysis of chemical constituents of polar extract of Toddalia asiatica root bark by LC-Q-TOF[J]. China J Tradit Chin Med Pharm,2019,34(12):5914-5919.
刘明,刘杨,邓颖,等. 飞龙掌血提取物对风寒湿佐剂性关节炎大鼠Th17/Treg平衡的影响[J]. 中药药理与临床,2018,34(3):108-111.
LIU M,LIU Y,DENG Y,et al. Effect of Dracaena asia-tica blood extract on Th17/Treg balance in rats with adjuvant arthritis due to wind-cold-dampness[J]. Pharmacol Clin Chin Mater Med,2018,34(3):108-111.
刘明,邓颖,刘杨,等. 飞龙掌血提取物对高脂血症心肌缺血小鼠氧化损伤的影响[J]. 中国比较医学杂志,2017,27(12):51-55.
LIU M,DENG Y,LIU Y,et al. Protective effects of Toddalia asiatica extract on oxidative damages in mice with myocardial ischemia and hyperlipidemia[J]. Chin J Comp Med,2017,27(12):51-55.
唐娟,李琴,刘娣佳,等. 民族药飞龙掌血提取物抗动脉粥样硬化作用研究[J]. 辽宁中医药大学学报,2023,25(5):28-33.
TANG J,LI Q,LIU D J,et al. Study on effects of ethnic medicine Toddalia asiatica(L.) Lam. extract against athe-rosclerosis[J]. J Liaoning Univ Tradit Chin Med,2023,25(5):28-33.
HOFBAUER T M,ONDRACEK A S,MANGOLD A,et al. Neutrophil extracellular traps induce MCP-1 at the culprit site in ST-segment elevation myocardial infarction[J]. Front Cell Dev Biol,2020,8:564169.
CHEN Y R,XIANG X D,SUN F,et al. Simvastatin reduces NETosis to attenuate severe asthma by inhibiting PAD4 expression[J]. Oxid Med Cell Longev,2023,2023:1493684.
ZHAO X Y,ZHANG L Y,LIU X,et al. Exogenous hydrogen sulfide inhibits neutrophils extracellular traps formation via the HMGB1/TLR4/p-38 MAPK/ROS axis in hyperhomocysteinemia rats[J]. Biochem Biophys Res Commun,2021,537:7-14.
LIN T T,SUNG Y L,SYU J Y,et al. Anti-inflammatory and antiarrhythmic effects of beta blocker in a rat model of rheumatoid arthritis[J]. J Am Heart Assoc,2020,9(18):e016084.
WANG K,ZHANG D M,LIU Y,et al. Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation,synovial hyperplasia,and cartilage destruction in rats[J]. Arthritis Res Ther,2018,20(1):43.
LI X Y,LU X C,FAN D P,et al. Synergistic effects of Erzhi pill combined with methotrexate on osteoblasts mediated via the Wnt1/LRP5/β-catenin signaling pathway in collagen-induced arthritis rats[J]. Front Pharmacol,2020,11:228.
安合定,张海燕,李玉祥,等. 维生素D对老龄大鼠超负荷诱导的骨骼肌肥大及维生素D受体表达的影响[J]. 第二军医大学学报,2016,37(8):1023-1027.
AN H D,ZHANG H Y,LI Y X,et al. Effect of vitamin D on overload-induced hypertrophy of skeletal muscle and expression of vitamin D receptor in aged rats[J]. Acad J Second Mil Med Univ,2016,37(8):1023-1027.
OZEN G,DELL’ANIELLO S,PEDRO S,et al. Re-duction of cardiovascular disease and mortality versus risk of new-onset diabetes mellitus with statin use in patients with rheumatoid arthritis[J]. Arthritis Care Res,2023,75(3):597-607.
CARBONE F,BONAVENTURA A,LIBERALE L,et al. Atherosclerosis in rheumatoid arthritis:promoters and opponents[J]. Clin Rev Allergy Immunol,2020,58(1):1-14.
DERKSEN V F A M,HUIZINGA T W J,VAN DER WOUDE D. The role of autoantibodies in the pathophy-siology of rheumatoid arthritis[J]. Semin Immunopathol,2017,39(4):437-446.
FOUSERT E,TOES R,DESAI J. Neutrophil extracellular traps(NETs)take the central stage in driving autoimmune responses[J]. Cells,2020,9(4):915.
CARROLL M B. Tocilizumab in the treatment of myocardial infarction[J]. Mod Rheumatol,2018,28(5):733-735.
LATIC N,ERBEN R G. Interaction of vitamin D with peptide hormones with emphasis on parathyroid hormone,FGF23,and the renin-angiotensin-aldosterone system[J]. Nutrients,2022,14(23):5186.
KIM D H,MEZA C A,CLARKE H,et al. Vitamin D and endothelial function[J]. Nutrients,2020,12(2):575.
COSENTINO N,CAMPODONICO J,MILAZZO V,et al. Vitamin D and cardiovascular disease:current evidence and future perspectives[J]. Nutrients,2021,13(10):3603.
0
浏览量
4
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构