玻璃酸钠分子量差异影响骨关节炎临床治疗获益的效应及机制分析

Differences in the molecular weight of sodium hyaluronate for osteoarthritis:benefits and mechanisms

玻璃酸钠是关节软骨和关节滑液的主要成分之一,对维持关节结构和功能具有重要的生理作用。关节内玻璃酸钠含量及理化性质异常是导致骨关节炎的病理机制之一,补充具有正常理化性质的外源性玻璃酸钠已成为目前骨关节炎临床治疗的常用策略。但对其临床获益也存在诸多争议。多项临床指南对关节内注射玻璃酸钠治疗骨关节炎的临床应用存在不同的表述。日益增多的研究和对既往研究的回顾分析提示,玻璃酸钠的分子量不同是影响其治疗骨关节炎临床获益的重要因素。不同玻璃酸钠产品具有不同的理化和生物学特点,可能产生不同的临床疗效和安全性事件。高分子量玻璃酸钠的糖链长度和交联程度与低分子量产品有显著差异,因此其理化性质、流变学特征、生理活性等也显示出差异性。一般来说,高分子量玻璃酸钠产品的黏性和弹性较高;与正常关节滑液中玻璃酸钠分子量较为接近的产品其流变学特征也较为相似。临床研究证实,高分子量玻璃酸钠产品多显示出明确的临床疗效和良好的安全性,可显著缓解患者关节疼痛及改善关节功能;而低分子量玻璃酸钠产品的临床疗效则不明确,部分研究中其疗效并未优于安慰剂。分子机制研究显示,玻璃酸钠的部分重要生理功能的发挥呈分子量依赖性,高分子量玻璃酸钠产品对免疫炎症的调节和胞外基质结构的改善作用可能更为显著。对玻璃酸钠分子量差异影响膝关节骨关节炎疗效的文献进行综述,有利于阐述玻璃酸钠的结构、理化性质及生物学功能,进一步优化玻璃酸钠治疗骨关节炎的临床应用方案。

Sodium hyaluronate is one of the natural components of articular cartilage and synovial fluid, which plays important roles in maintaining the structure and physiological functions of joints. Abnormal change of the content and physicochemical properties of sodium hyaluronate in the joints is one of the common pathological causes of osteoarthritis. Supplementation of exogenous sodium hyaluronate, which has similar physical and chemical properties as those in normal joints, has been considered as an effective strategy for clinical treatment of osteoarthritis. However, the benefits of intra-articular injection of sodium hyaluronate are still under debates. Moreover, different recommendations for clinical use were developed in several clinical guidelines. Several guidelines suggested that molecular weight of sodium hyaluronate was an important factor influencing the clinical benefits in osteoarthritis. Diverse products of sodium hyaluronate present different physicochemical and biological characteristics, which may lead to differences in clinical efficacy and safety. High-molecular-weight sodium hyaluronate, with highly modified and cross-linked sugar chains, potentially differ from those with low molecular weight in physicochemical properties, rheological characteristics, and physiological activities. In general, high-molecular-weight sodium hyaluronate have higher viscosity and elasticity. The exogenous hyaluronate, of which the molecular weight is similar to those in normal joints, probably have the similar rheological characteristics. A large number of clinical studies demonstrated that sodium hyaluronate products with high-molecular weight significantly relieved joint pain and improved joint functions in patients with osteoarthritis. In contrast, the clinical efficacy of the low-molecular-weight hyaluronate is still controversial, because several studies could not establish the superiority in osteoarthritis when comparing with the placebo. Studies on molecular mechanisms revealed that some physiological functions of sodium hyaluronate were molecular-weight dependent. High-molecular-weight sodium hyaluronate may have more pronounced impacts on the regulation of inflammation and maintaining the homeostasis of extracellular matrix. This review focused on the effects of sodium hyaluronate with different molecular weight in treating osteoarthritis. Evidence based on clinical studies related to the molecular-weight differences of sodium hyaluronate were presented. Furthermore, the optimal use of various products of sodium hyaluronate with different molecular weight was discussed.