红芪杂多糖及其透明质酸水凝胶对大鼠骨关节炎的治疗作用
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摘要
目的探讨红芪杂多糖(HHG-2)及其透明质酸水凝胶对大鼠骨关节炎(osteoarthritis,OA)的治疗作用。方法将Wistar大鼠随机分组,采用木瓜蛋白酶复制OA动物模型,经HHG-2及其透明质酸水凝胶的干预,测定关节活动范围、关节滑膜病理变化及其中糖胺多糖、关节灌洗液中炎性细胞及炎症因子等指标,对HHG-2及其透明质酸水凝胶治疗OA的作用及机制进行研究。结果 HHG-2(1周2次局部注射0.36、0.12 mg·joint-1)及其透明质酸水凝胶(1周1次局部注射0.24 mg·joint-1HHG-2的透明质酸水凝胶)能明显扩大OA大鼠膝关节的伸展角度,改善关节病理变化,减小关节滑膜厚度,提高滑膜中糖胺多糖的含量;同时HHG-2及其透明质酸水凝胶可降低关节灌洗液中炎性细胞及IL-1β、IL-6、TNF-α水平(P<0.05,P<0.01)。结论 HHG-2及其透明质酸水凝胶对OA有明显的治疗作用,而缓解局部炎症反应是其作用机制之一。同时,实验结果提示HHG-2透明质酸水凝胶治疗OA可减少给药次数,提高患者的依从性而提高临床疗效。
This study was performed to investigate the therapeutic effects of Hedysari Heteropoly(HHG-2)and hyaluronic acid hydrogel on osteoarthritis(OA) in rats. OA animal model was constructed by using papain in Wistar rats. After the interference of HHG-2 and hyaluronic acid hydrogel, we measured the range of joint activity,the pathological changes of synovial synovium and the indexes of glucosamine polysaccharide, inflammatory cells and inflammatory factors in the joint lavage fluid for evaluating the effect and mechanism of HHG-2 on OA. Data showed that HHG-2 and hyaluronic acid hydrogel could significantly expand the extension angle, improve the pathological changes of the joints, reduce the thickness of synovial membrane, and increase the glycosaminoglycan in the synovium of the knee joint in OA rats. At the same time, HHG-2 and hyaluronic acid hydrogel decreased the levels of inflammatory cells and IL-1 beta, IL-6 and TNF-alpha in joint lavage fluid(P<0.05, 0.01). Taken together, HHG-2 and hyaluronic acid hydrogel have certain therapeutic effects on OA, and one of the mechanisms is relieving local inflammatory response. Meanwhile,HHG-2 hyaluronic acid hydrogel can reduce the frequency of administration, improve the compliance of patients and improve the clinical efficacy of OA.
This study was performed to investigate the therapeutic effects of Hedysari Heteropoly(HHG-2)and hyaluronic acid hydrogel on osteoarthritis(OA) in rats. OA animal model was constructed by using papain in Wistar rats. After the interference of HHG-2 and hyaluronic acid hydrogel, we measured the range of joint activity,the pathological changes of synovial synovium and the indexes of glucosamine polysaccharide, inflammatory cells and inflammatory factors in the joint lavage fluid for evaluating the effect and mechanism of HHG-2 on OA. Data showed that HHG-2 and hyaluronic acid hydrogel could significantly expand the extension angle, improve the pathological changes of the joints, reduce the thickness of synovial membrane, and increase the glycosaminoglycan in the synovium of the knee joint in OA rats. At the same time, HHG-2 and hyaluronic acid hydrogel decreased the levels of inflammatory cells and IL-1 beta, IL-6 and TNF-alpha in joint lavage fluid(P<0.05, 0.01). Taken together, HHG-2 and hyaluronic acid hydrogel have certain therapeutic effects on OA, and one of the mechanisms is relieving local inflammatory response. Meanwhile,HHG-2 hyaluronic acid hydrogel can reduce the frequency of administration, improve the compliance of patients and improve the clinical efficacy of OA.
引文
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[17]何薇,赵峰,张国平,等.透明质酸对骨关节炎软骨细胞白细胞介素-1β及肿瘤坏死因子-α表达的影响[J].中国老年学杂志,2017,37(1):25-27.
[18]Haseeb A,Ansari M Y,Haqqi T M.Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes[J].J Orthop Res,2017,35(2):311-320.
[19]陈英,张文玲,黄涛,等.炎症因子TNF-α、IL-6、IL-17与类风湿关节炎并发动脉粥样硬化的关系[J].免疫学杂志,2017,33(3):268-272.
[2]肖壮,唐涛,孙先润,等.骨关节炎治疗药物的研究进展[J].中国药房,2016,27(35):5037-5040.
[3]国家药典委员会.中国药典一部[S].北京:中国医药科技出版社,2010:142.
[4]吴普,孙星衍,孙冯翼,等.神农本草经[M].北京:科学技术文献出版社,2003:25.
[5]王希玉,路莉,胡燕,等.不同红芪多糖抗肿瘤和免疫调节作用研究[J].中药药理与临床,2009,25(5):72-74.
[6]李菲,卫东锋,张俊英,等.红芪多糖对人肺腺癌A549细胞蛋白表达图谱影响的研究[J].中药药理与临床,2014,30(4):54-59.
[7]赵良功,李晓东,赵建辉,等.4种红芪多糖对实验性糖尿病小鼠血糖的影响[J].中药材,2009,32(10):1590-1592.
[8]梁克玉.关节内注射透明质酸治疗骨性关节炎近3年研究进展[J].中国骨伤,2010,23(12):962-964.
[9]方芳,邹来勇,汤群珍.牛膝多糖对兔膝关节骨性关节炎修复的影响[J].河北中医,2014,36(5):749-750,755.
[10]胡爱心,陈廖斌,汪晖,等.黄芪多糖对大鼠骨关节炎的影响[J].武汉大学学报(医学版),2008,29(2):157-161,285.
[11]付长龙,刘献祥.中药多糖干预骨关节炎作用机制探讨[J].风湿病与关节炎,2015,4(3):36-39.
[12]赵峰,何薇,刘桂兰,等.透明质酸水凝胶修复大鼠软骨缺损的实验研究[J].重庆医学,2014,43(35):4719-4722.
[13]王红权,詹杰.白细胞介素家族在骨关节炎中的表达意义[J].现代免疫学,2016,36(3):261-264.
[14]Bahtiar A,Nurazizah M,Roselina T,et al.Ethanolic extracts of babandotan leaves(Ageratum conyzoides,L.)prevents inflammation and proteoglycan degradation by inhibiting TNF-αand MMP-9 on osteoarthritis rats induced by monosodium iodoacetate[J].Asian Pac J Trop Med,2017,10(3):256-262.
[15]Bucher H,Mang S,Keck M,et al.Neutralization of both IL-1α/IL-1βplays a major role in suppressing combined cigarette smoke/virus-induced pulmonary inflammation in mice[J].Pulm Pharmacol Ther,2017,44:96-105.
[16]Silva LR,Alves AF,Cavalcante-Silva LHA,et al.Milonine,a morphinandienone alkaloid,has anti-inflammatory and analgesic effects by inhibiting TNF-αand IL-1βproduction[J].Inflammation,2017,40(6):2074-2085.
[17]何薇,赵峰,张国平,等.透明质酸对骨关节炎软骨细胞白细胞介素-1β及肿瘤坏死因子-α表达的影响[J].中国老年学杂志,2017,37(1):25-27.
[18]Haseeb A,Ansari M Y,Haqqi T M.Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes[J].J Orthop Res,2017,35(2):311-320.
[19]陈英,张文玲,黄涛,等.炎症因子TNF-α、IL-6、IL-17与类风湿关节炎并发动脉粥样硬化的关系[J].免疫学杂志,2017,33(3):268-272.