“杜仲-当归”介导Wnt/β-catenin信号转导调控MMP-13表达防治关节炎的作用机制研究

目的 研究“杜仲-当归”介导Wnt/β-catenin信号转导调控MMP13表达防治骨性关节炎（osteoarthritis,OA）的作用机制。方法 取SD大鼠,随机分为Sham组、OA组、OA+补肾组（杜仲40 mg·kg^-1）、OA+活血组（当归40 mg·kg^-1）、OA+补肾活血组（杜仲-当归药液40 mg·kg^-1）、OA+阳性药物组（西乐葆10 mg·kg^-1+奥泰灵1.2 mg·kg^-1）共6组。OA模型制备成功后,各组大鼠给予对应药物治疗,连续给药8周。番红O染色检测软骨组织变化,免疫组织化学检测软骨组织中MMP-13表达,ELISA检测大鼠血清IL-6、IL-8含量,Western blotting检测软骨组织中MMP-3、MMP-9、MMP-13、β-catenin蛋白表达。分离正常SD大鼠软骨细胞,IL-1β（10 ng·mL^-1）干预诱导体外OA炎症模型并进行药物干预。番红O染色检测软骨细胞表型变化,ELISA检测软骨细胞IL-6、IL-8含量,免疫荧光染色检测软骨细胞β-catenin表达,qRT-PCR检测软骨细胞中IL-6、IL-8、MMP-3、MMP-9和MMP-13的mRNA表达,Western blotting检测软骨细胞中MMP-3、MMP-9、MMP-13、β-catenin蛋白表达。结果 药物处理对OA导致的软骨组织损伤有不同程度的修复作用;杜仲-当归可下调血清中IL-6、IL-8水平,下调软骨组织中MMP-3、MMP-9、MMP-13、b-catenin的蛋白表达。与IL-1b组相比,杜仲-当归可提高软骨细胞存活率,改善细胞形态,下调软骨细胞IL-6、IL-8水平,降低软骨细胞中b-catenin荧光强度,并下调软骨细胞中IL-6、IL-8、MMP-3、MMP-9、MMP-13的mRNA表达和MMP-3、MMP-9、MMP-13、b-catenin的蛋白表达。结论 体内、体外试验表明补肾活血中药“杜仲-当归”可以通过促进软骨细胞增殖、调控炎症因子水平、改善软骨基质降解、改善软骨病理损伤起到对OA的防治作用,且作用机制可能与介导Wnt/β-catenin信号转导调控MMP-13表达有关。     

LC-MS结合网络药理学探讨“片姜黄-当归”挥发油防治膝骨关节炎的作用机制

目的 提取“片姜黄-当归”药对挥发油,使用液相色谱-质谱联用仪(LC-MS)对提取的挥发油进行化学成分定性分析,并运用网络药理学探讨药对挥发油防治膝骨关节炎(knee osteoarthritis,KOA)的作用机制。方法 采用水蒸气蒸馏法提取“片姜黄-当归”药对挥发油,并使用LC-MS对挥发油成分进行分析。借助Pubchem、Swiss Target Prediction、GeneCards、DAVID等数据库预测有效成分防治KOA的作用靶点及通路,对核心基因进行基因本体(Gene ontology,GO)分析与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,并使用Cytoscape软件构建“活性成分-疾病靶点”可视化网络图。运用AutoDock及Pymol对度值靠前的靶点与活性成分进行分子对接验证。结果 “片姜黄-当归”药对挥发油中共鉴定出59种化合物,主要成分为莪术酮、异姜黄醇、藁本内酯等;通过网络药理学筛选出挥发油作用于KOA的28个潜在靶点,包括CTSK、PTGS1、PTGS2和ESR1等关键靶点;KEGG富集分析预测“片姜黄-当归”药对挥发油主要通过肿瘤坏死因子信号通路、破骨细胞分化、白介素17信号通路、松弛素信号通路、丝裂原活化蛋白激酶信号通路来发挥治疗KOA的作用。分子对接结果显示筛选的活性成分与其对应靶蛋白均具有较好的结合活性。结论 使用LC-MS结合网络药理学的方法初步探明了“片姜黄-当归”药对挥发油中的主要有效成分及其干预KOA的潜在靶点与作用机制,为“片姜黄-当归”后续的深入研究提供思路。     

p38丝裂原活化蛋白激酶抑制剂对大鼠骨关节炎软骨细胞凋亡的影响

目的 观察p38丝裂原活化蛋白激酶(p38MAPK)抑制剂SB203580对大鼠骨关节炎(OA)软骨细胞凋亡的影响.方法 40只SD大鼠随机分为四组,A、B、C组行单侧膝关节前交叉韧带切除术(ACLT),A组于术后行关节腔内注射0.1 ml的SB203580(100 um/L),B组注射等量生理盐水(实验对照),C组不予任何处理(空白对照组),D组为正常对照组.术后8周处死动物.观察各组标本大体评分、病理组织学改变、软骨细胞凋亡指数.结果 A组病理组织学改变轻于B、C组,各组均发现有软骨细胞凋亡.D组凋亡指数与其他三组比较,P均<0.05.A组的凋亡指数低于B、C组(P均<0.05).结论 ACLT可以导致大鼠OA的软骨细胞凋亡增加,关节腔内注射p38MAPK抑制剂能有效抑制其软骨细胞凋亡.     

A systematic review on changed biomechanics of lower extremities in obese individuals: a possible role in development of osteoarthritis

Obesity has been identified as a risk factor for osteoarthritis. For the weight‐bearing joints, the combination of increased load and changed joint biomechanics could be regarded as underlying principle for this relation. This systematic review of the literature focused on the differences between obese and normal‐weight subjects in biomechanics of the hip, knee and ankle joint during every day movements to summarize differences in joint load due to both higher body weight and differences in movement patterns. A systematic search, up to November 2010, was performed in the Pubmed and Embase databases. This review showed that obese individuals adjust their movement strategy of every day movements. At self‐selected speed, obese individuals walked slower, with shorter and wider steps, had longer stance duration and had a greater toe‐out angle compared with normal‐weight individuals. Obese sit‐to‐stand movement was characterized by less hip flexion and greater foot displacement. Obese individuals showed altered biomechanics during every day movements. These altered biomechanics could be related to the initiation of osteoarthritis by a change in the load‐bearing regions of the articular cartilage in the weight‐bearing joints.     

Treatment of osteoarthritis in hypertensive patients

Importance of the field: Osteoarthritis and hypertension commonly co-exist. Treatment of osteoarthritis in hypertensive patients is a therapeutic challenge due to the adverse effects of some analgesics, especially non-steroidal anti-inflammatory drugs (NSAIDs), on blood pressure. Even small drug-induced rises in blood pressure due to therapy may significantly increase cardiovascular risk in these patients if sustained over the long term. Patients treated with certain classes of antihypertensive agent may be at particular risk of deterioration in blood pressure control with NSAID therapy. NSAIDs may also increase cardiovascular risk due to mechanisms other than by raising blood pressure.

Areas covered in this review: We discuss the management of osteoarthritis in the hypertensive patient, review the evidence for the effects of paracetamol and NSAIDs on blood pressure and discuss novel therapeutic strategies for osteoarthritis that might diminish this problem. A literature search was undertaken in PubMed including the years 1980 – 2009.

What the reader will gain: Insight will be gained into the complexity of treating patients with co-existent osteoarthritis and hypertension and into possible new approaches to treating osteoarthritis symptoms effectively in these patients while minimising any adverse impact on blood pressure control.

Take home message: There are ways to minimise the adverse impact of treatment of osteoarthritis on blood pressure control in hypertensive patients.     

Ulnar Neuropathy in Bicyclists

In brief: A common overuse injury associated with bicycling is ulnar neuropathy (handlebar palsy). The cyclist will notice the onset of numbness, weakness, and loss of coordination in one or both hands, usually after several days of cycling. Several corrective measures are suggested, including well-padded bicycling gloves, padded handlebars, correct frame size, correct distance from seat to stem, and frequent changing of hand position on the handlebars. If the pain cannot be alleviated by these measures, the cyclist should stop until improvement occurs.