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类风湿关节炎的发病机制与当前治疗策略:一篇系统综述文章

Pathogenesis and Current Treatment Strategies in Rheumatoid Arthritis: A Systematic Review Article.

作者信息

Deka Debajani

机构信息

Department of Anatomy, Pragjyotishpur Medical College and Hospital, Guwahati, Assam, India.

出版信息

Ann Afr Med. 2025 Jul 1;24(3):532-539. doi: 10.4103/aam.aam_11_24. Epub 2025 May 2.

Abstract

Rheumatoid arthritis (RA) is a chronic, symmetrical, and inflammatory autoimmune disease that initially affects small joints, progressing to larger joints, and eventually the skin, eyes, heart, kidneys, and lungs. It has been recorded that RA affects 0.5%-1% of the adult population of developed regions. It initially affects small joints, progressing to larger joints, and eventually the skin, eyes, heart, kidneys, and lungs. Often, the bone and cartilage of joints are destroyed, and tendons and ligaments weaken. All this damage to the joints causes deformities and bone erosion, usually very painful for a patient. RA by producing inflammatory cytokines and proteinases, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases that perpetuate joint destruction by abnormal proliferation of synovium. Under the influence of synovial cells, cytokines such as - Interleukin (IL)-1 and IL-17 chondrocytes are destroyed by apoptosis. Again the extracellular matrix secretes a proteinase called MMPs that damages the type 2 collagen fibers of the cartilage matrix causing biomechanical changes to the joint movements. This way with destruction of articular cartilage of the joint surface by hyperplastic synovium leads to a reduction of joint space. The difference between the hyaline cartilage of the articular surface and other hyaline cartilage is that articular hyaline cartilage never undergoes regeneration. With limited membrane permeability and poor gastrointestinal stability, monoclonal antibodies (mABs) do not have good oral bioavailability (<1%). For this reason, they are usually not administered orally, and parenteral administration is mostly by intravenous, subcutaneous (SC), and intramuscular (IM) injections. When mABs are injected IM or SC, the absorption process from the site of injection is through the interstitial space and into the lymphatic system, with subsequent draining into the systemic circulation. Although IM and SC routes of administration offer lower bioavailability because of proteolytic degradation in the interstitial fluid or the lymphatic system, the SC route is the most widely used due to convenience and the possibility of patient self-administration. For these last two routes of administration, the peak plasma concentration after a single dose is achieved 3-7 days after administration, due to the slow absorption into the systemic circulation. Other potential routes of administration include intravitreal, intraperitoneal, and pulmonary. CRD NUMBER-42024601637.

摘要

类风湿性关节炎(RA)是一种慢性、对称性炎性自身免疫性疾病,最初累及小关节,随后发展至大关节,最终可影响皮肤、眼睛、心脏、肾脏和肺部。据记载,RA在发达地区影响0.5%-1%的成年人口。它最初累及小关节,随后发展至大关节,最终可影响皮肤、眼睛、心脏、肾脏和肺部。通常,关节的骨骼和软骨会遭到破坏,肌腱和韧带会变弱。关节的所有这些损伤会导致畸形和骨质侵蚀,患者通常会感到非常疼痛。RA通过产生炎性细胞因子和蛋白酶,如基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂,使滑膜异常增殖,从而使关节破坏持续存在。在滑膜细胞的影响下,诸如白细胞介素(IL)-1和IL-17等细胞因子会使软骨细胞通过凋亡被破坏。此外,细胞外基质会分泌一种名为MMPs的蛋白酶,它会破坏软骨基质的Ⅱ型胶原纤维,导致关节运动的生物力学变化。这样,增生的滑膜破坏关节表面的关节软骨,导致关节间隙变窄。关节表面的透明软骨与其他透明软骨的不同之处在于,关节透明软骨从不进行再生。由于膜通透性有限且胃肠道稳定性差,单克隆抗体(mABs)的口服生物利用度不佳(<1%)。因此,它们通常不通过口服给药,肠胃外给药大多通过静脉注射、皮下注射(SC)和肌肉注射(IM)。当mABs通过IM或SC注射时,从注射部位的吸收过程是通过组织间隙进入淋巴系统,随后排入体循环。尽管IM和SC给药途径由于在组织液或淋巴系统中的蛋白水解降解而具有较低的生物利用度,但由于方便且患者可自行给药,SC途径是最广泛使用 的。对于这最后两种给药途径,单剂量给药后血浆峰浓度在给药后3-7天达到,这是由于吸收进入体循环的速度较慢。其他潜在的给药途径包括玻璃体内、腹腔内和肺部给药。CRD编号-42024601637。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e56/12380159/acdcbbb7ce4a/AAM-24-532-g001.jpg

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