[1]李仪杰,王丽欢,潘赐明,等.肾茶治疗痛风性关节炎的作用机制研究[J].中国中医骨伤科杂志,2023,31(05):12-17+23.[doi:10.20085/j.cnki.issn1005-0205.230503]
 LI Yijie,WANG Lihuan,PAN Ciming,et al.Mechanism of Clerodendranthus Spicatus on the Treatment of Gouty Arthritis[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2023,31(05):12-17+23.[doi:10.20085/j.cnki.issn1005-0205.230503]
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肾茶治疗痛风性关节炎的作用机制研究()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第31卷
期数:
2023年05期
页码:
12-17+23
栏目:
实验研究
出版日期:
2023-05-15

文章信息/Info

Title:
Mechanism of Clerodendranthus Spicatus on the Treatment of Gouty Arthritis
文章编号:
1005-0205(2023)05-0012-06
作者:
李仪杰12王丽欢12潘赐明12杨焕1梁家榕1叶斌1△
1云南中医药大学(昆明,650500)
2云南中医药大学中药学院暨云南省南药可持续利用研究重点实验室
Author(s):
LI Yijie12WANG Lihuan12PAN Ciming12YANG Huan1LIANG Jiarong1YE Bin1△
1Yunnan University of Chinese Medicine,Kunming 650500,China;
2School of Traditional Chinese Medicine,Yunnan University of Chinese Medicine and Yunnan Key Laboratory of Sustainable Utilization of Southern Medicine,Kunming 650500,China.
关键词:
肾茶 痛风性关节炎 软骨 尿酸单钠晶体
Keywords:
clerodendranthus spicatus gouty arthritis cartilage monosodium urate crystals
分类号:
R-33
DOI:
10.20085/j.cnki.issn1005-0205.230503
文献标志码:
A
摘要:
目的:探讨肾茶治疗痛风性关节炎大鼠模型的相关作用机制。方法:选取40只雄性SD大鼠并适应性饲养1周,随机分为空白组、模型组、秋水仙碱组、肾茶高、低剂量组,每组8只,除空白组和模型组进行生理盐水7 d灌胃干预,其余各组分别用秋水仙碱、肾茶高、低剂量水煎剂灌服。在干预5 d后采用改良的Coderre方法对大鼠右侧踝关节进行尿酸单钠晶体注射造模,在造模后4~12 h发现大鼠踝关节有明显的肿胀和功能障碍确认造模成功。各组大鼠分别在造模后4,10,24,36,48 h进行踝关节功能障碍指数及肿胀情况评估,并在造模48 h后,检测血清和滑膜组织中白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α的浓度,踝关节软骨组织中COL2、MMP-13、MMP-3蛋白表达,并观察大鼠踝关节软骨病理情况。结果:模型组大鼠关节肿胀程度和功能障碍指数明显高于空白组,差异有统计学意义(P<0.01); 与模型组比,肾茶高剂量组和秋水仙碱组大鼠踝关节功能障碍指数较低肿胀度较轻,差异有统计学意义(P<0.05)。肾茶高剂量组和秋水仙碱组大鼠血清中白细胞介素-6和滑膜中的白细胞介素-1β、肿瘤坏死因子-α的浓度炎性因子均显著低于模型组,差异有统计学意义(P<0.05); 肾茶高剂量组与秋水仙碱组中炎性因子的表达水平差异无统计学意义(P>0.05); 同时肾茶高剂量组与秋水仙碱组显著抑制MMP-13及MMP-3蛋白表达,增加COL2表达,差异有统计学意义(P<0.05),而秋水仙碱组对增加COL2表达不显著,差异无统计学意义(P>0.05),且肾茶抑制炎性因子和与细胞外基质降解相关的酶表达都具有剂量依赖性; 相对于模型组,肾茶高剂量组的大鼠踝关节软骨表面比较平滑,或有少量的毛糙样改变,且肾茶高剂量组的治疗效果优于秋水仙碱组。结论:肾茶可以通过抑制MMP-13和MMP-3表达及炎症反应减轻尿酸单钠诱导的软骨基质降解,起到保护关节软骨的作用,还能缓解痛风性关节炎大鼠的关节肿胀和功能障碍。
Abstract:
Objective:To investigate the mechanism related to Clerodendranthus spicatus on the treatment of gouty arthritis.Methods:40 male SD rats were selected and fed adaptively for one week,and they were randomly divided into blank group,model group,colchicine group,Clerodendranthus spicatus high-dose and low-dose groups with 8 rats in each group.Gastrointestinal intervention was carried out for 7 d,and the others were fed with colchicine,Clerodendranthus spicatus high-dose and low-dose water decoction.The modified Coderre method was used to inject monosodium urate(MSU)crystals into the right ankle joint of the rats to create a model on the 5th day of intervention.The model was established after 4 to 12 h.It was found that the ankle joint of the rat had obvious swelling and dysfunction.The rats were evaluated for ankle joint dysfunction index and swelling at 4,10,24,36,and 48 h after modeling,and interleukin-6,interlein-1β and tumor necrosis factor-α concentrations in serum and synovial tissue were detected 48 hours after modeling,so as COL2,MMP-13,MMP-3 protein expression in ankle cartilage tissue and pathological conditions of rat ankle cartilage.Results:The joint swelling degree and dysfunction index of rats in the model group were significantly higher than those in the blank group(P<0.01),and the ankle joint dysfunction index and swelling degree of the rats in the high-dose Clerodendranthus spicatus group and the colchicine group were significantly reduced compared with the model group(P<0.05).The interleukin-6 in the serum of rats in the high-dose Clerodendranthus spicatus group and the colchicine group and the concentrations of interleukin-1β and tumor necrosis factor-α in the synovium were significantly lower than model group(P<0.05),and there was no significant difference in the expression levels of inflammatory factors between the Clerodendranthus spicatus high-dose group and the colchicine group(P>0.05).The expressions of MMP-13 and MMP-3 proteins of the Clerodendranthus spicatus high-dose group and colchicine group were significantly inhibited,and the expressions of COL2 were increased(P<0.05),while the expressions of COL2 the colchicine group were not significantly increase(P>0.05),and Clerodendranthus spicatus inhibited the expressions of inflammatory factors and enzymes related to extracellular matrix degradation in a dose-dependent manner.The surface of rat ankle articular cartilage in the high-dose Clerodendranthus spicatus group was smoother or had a small amount of roughness compared with the model group.The therapeutic efficacy of the high-dose Clerodendranthus spicatus group was better than the colchicine group.Conclusion:Clerodendranthus spicatus can inhibite the expressions of MMP-13 and MMP-3 and inflammatory response can reduce the degradation of cartilage matrix induced by MSU,protect cartilage,and relieve joint swelling and dysfunction in rats with gouty arthritis.

参考文献/References:

[1] DEHLIN M,JACOBSSON L,RODDY E.Global epidemiology of gout:prevalence,incidence,treatment patterns and risk factors[J].Nature Reviews Rheumatology,2020,16(7):380-390.
[2] BOKHARI R A,TANTOWI N,LAU S F,et al.Java Tea(Orthosiphon stamineus)protected against osteoarthritis by mitigating inflammation and cartilage degradation:a preclinical study[J].Inflammopharmacology,2018,26(4):939-949.
[3] 谢招虎,狄朋桃,李兆福.猫须草治疗痛风的机制研究进展[J].中国中医基础医学杂志,2019,25(6):860-863.
[4] ZHU F,YIN L,JI L,et al.Suppressive effect of Sanmiao formula on experimental gouty arthritis by inhibiting cartilage matrix degradation:an in vivo and in vitro study[J].International Immunopharmacology,2016,30:36-42.
[5] 王永涛,谢一舟,樊效鸿,等.加味当归四逆汤对膝骨关节炎大鼠软骨退变的影响及作用机制研究[J].中国中医骨伤科杂志,2022,30(11):7-12.
[6] 张永怡,吴家超,李水萍,等.民族药肾茶的化学成分与药理作用研究进展[J].中医药学报,2021,49(1):112-120.
[7] 丘青中,戚子荣,邢振龙.萆薢祛风饮用于湿热蕴结证痛风性关节炎大鼠的疗效及机制研究[J].中国医药导报,2021,18(13):19-22.
[8] 徐东,朱小霞,曾学军,等.痛风诊疗规范[J].中华内科杂志,2020(6):421-426.
[9] 赵景峰,张诗元,王大海,等.王耀光教授治疗痛风性关节炎临床经验总结[J].天津中医药,2022,39(6):706-709.
[10] 赵应红,林艳芳,张丽丽,等.傣药芽糯妙(肾茶)的研究与应用[J].中国民族医药杂志,2008,14(10):72-77.
[11] ASHRAF K,SULTAN S,ADAM A.Orthosiphon stamineus Benth is an outstanding food medicine:review of phytochemical and pharmacological activities[J].Journal of Pharmacy & Bioallied Sciences,2018,10(3):109-118.
[12] DALBETH N,GOSLING A L,GAFFO A,et al.Gout[J].Lancet(London,England),2021,397(10287):1843-1855.
[13] JHANG J J,LIN J H,YEN G C.Beneficial properties of phytochemicals on nlrp3 inflammasome-mediated gout and complication[J].Journal of Agricultural and Food Chemistry,2018,66(4):765-772.
[14] ROCK K L,KATAOKA H,LAI J J.Uric acid as a danger signal in gout and its comorbidities[J].Nature Reviews Rheumatology,2013,9(1):13-23.
[15] XIE J,WANG Y,LU L,et al.Cellular senescence in knee osteoarthritis:molecular mechanisms and therapeutic implications[J].Ageing Research Reviews,2021,70:101413.
[16] CHHANA A,CALLON K E,POOL B,et al.Monosodium urate monohydrate crystals inhibit osteoblast viability and function:implications for development of bone erosion in gout[J].Ann Rheum Dis,2011,70(9):1684-1691.
[17] HWANG H S,YANG C M,PARK S J,et al.Monosodium urate crystal-induced chondrocyte death via autophagic process[J].Int J Mol Sci,2015,16(12):29265-29277.
[18] FINDLAY D M,ATKINS G J.Osteoblast-chondrocyte interactions in osteoarthritis[J].Current Osteoporosis Reports,2014,12(1):127-134.
[19] ZHANG Y,LI S,JIN P,et al.Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis[J].Nat Commun,2022,13(1):2447.
[20] Multidisciplinary Expert Task Force on Hyperuricemia and Related Diseases Chinese Multidisciplinary Expert Consensus on the Diagnosis and Treatment of Hyperuricemia and Related Diseases[J].Chinese Medical Journal,2017,130(20):2473-2488.
[21] SHU C C,FLANNERY C R,LITTLE C B,et al.Catabolism of fibromodulin in developmental rudiment and pathologic articular cartilage demonstrates novel roles for MMP-13 and ADAMTS-4 in C-terminal processing of SLRPs[J].Int J Mol Sci,2019,20(3):579.
[22] VAN GEFFEN E W,VAN CAAM A P M,SCHREURS W,et al.IL-37 diminishes proteoglycan loss in human OA cartilage:donor-specific link between IL-37 and MMP-3[J].Osteoarthritis and Cartilage,2019,27(1):148-157.
[23] MALEMUD C J.Inhibition of MMPs and ADAM/ADAMTS[J].Biochemical Pharmacology,2019,165:33-40.
[24] MULYAD I,SUNNAT I,AZHARY M,et al.The correlation of age and body mass index with the level of both protease MMP3 and anti-protease TIMP-1 among Indonesian patients with chronic obstructive pulmonary disease:a preliminary findings[J].BMC Research Notes,2018,11(1):551.

备注/Memo

备注/Memo:
基金项目:云南省科技人才和平台计划(202105AG070012)
云南省南药可持续利用研究重点实验室开放课题(202105AG070012XS2240)
云南中医药大学高层次人才科学研究项目(GCC202205)
云南省教育厅科学研究基金项目(2023Y0432)
通信作者 E-mail:13917526797@163.com
更新日期/Last Update: 2023-05-10