Fujitsuka Naoki, Tamai Mitsuo, Tsuchiya Kazuaki, Iizuka Seiichi, Tsuchiya Naoko, Makino Bunsho, Hattori Tomohisa, Kase Yoshio, Isohama Yoichiro
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
Botanical Raw Materials Division, Botanical Raw Materials Research Laboratories, Tsumura & Co., Ami-machi, Ibaraki, 300-1192, Japan.
BMC Complement Altern Med. 2015 Dec 24;15:451. doi: 10.1186/s12906-015-0979-7.
Hydrarthrosis, which is associated with knee pain and limited range of motion, decreases the quality of life (QOL) of patients with osteoarthritis (OA). The Kampo medicine boiogito is prescribed for the treatment of knee OA with hydrarthrosis; however, its precise mechanisms of action remain unknown. The purposes of this study were to assess the pharmacological effects of boiogito and its mechanisms of action on joint effusion in rats with surgically induced OA.
A rat OA model was produced by transecting the anterior (cranial) cruciate ligament, medial collateral ligament, and medial meniscus in the right knee joints of 7-week-old female Wistar rats. The rats were given chow containing boiogito (1 or 2%) or indomethacin (0.002 %) for 4 weeks after surgical transection. Levels of interleukin-1β (IL-1β) and hyaluronic acid (HA) were measured by enzyme-linked immunosorbent assay. Knee joint pain was assessed using an incapacitance tester. Osmotic water permeability in cultured rabbit synovial cells was assessed using stopped-flow analysis.
Increased synovial fluid volume and knee joint pain were observed in rats with surgically induced OA. In rats with OA, levels of IL-1β and HA in the articular cavity were higher but concentration of HA in synovial fluid was lower than in sham-operated rats, suggesting excessive synovial fluid secretion. Administration of boiogito improved hydrarthrosis, IL-1β, and HA concentrations and alleviated knee joint pain in rats with OA. Indomethacin reduced IL-1β and knee joint pain but failed to improve hydrarthrosis or HA concentration in rats with OA. Osmotic water permeability in synovial cells, which is related to the function of the water channel aquaporin, was decreased by treatment with boiogito.
Boiogito ameliorates the increased knee joint effusion in rats with OA by suppressing pro-inflammatory cytokine IL-1β production in the articular cavity and regulating function of water transport in the synovium. The improvement of hydrarthrosis by boiogito results in the increased HA concentration in synovial fluid, thus reducing joint pain. Boiogito may be a clinically useful treatment of QOL in patients with OA with hydrarthrosis.
关节积水与膝关节疼痛及活动范围受限相关，会降低骨关节炎（OA）患者的生活质量（QOL）。汉方药物防己地黄汤被用于治疗伴有关节积水的膝关节OA；然而，其确切作用机制尚不清楚。本研究的目的是评估防己地黄汤对手术诱导的OA大鼠关节积液的药理作用及其作用机制。
通过切断7周龄雌性Wistar大鼠右膝关节的前（颅侧）交叉韧带、内侧副韧带和内侧半月板建立大鼠OA模型。手术切断后，给大鼠喂食含防己地黄汤（1%或2%）或吲哚美辛（0.002%）的饲料4周。通过酶联免疫吸附测定法测量白细胞介素-1β（IL-1β）和透明质酸（HA）的水平。使用失能测试仪评估膝关节疼痛。使用停流分析法评估培养的兔滑膜细胞中的渗透水通透性。
在手术诱导的OA大鼠中观察到滑液体积增加和膝关节疼痛。在OA大鼠中，关节腔中IL-1β和HA的水平较高，但滑液中HA的浓度低于假手术大鼠，提示滑液分泌过多。给予防己地黄汤可改善OA大鼠的关节积水、IL-1β和HA浓度，并减轻膝关节疼痛。吲哚美辛降低了IL-1β和膝关节疼痛，但未能改善OA大鼠的关节积水或HA浓度。用防己地黄汤处理可降低滑膜细胞中与水通道蛋白水通道功能相关的渗透水通透性。
防己地黄汤通过抑制关节腔中促炎细胞因子IL-1β的产生和调节滑膜中的水运输功能，改善OA大鼠膝关节积液增加的情况。防己地黄汤对关节积水的改善导致滑液中HA浓度增加，从而减轻关节疼痛。防己地黄汤可能是治疗伴有关节积水的OA患者生活质量的一种临床有用的疗法。
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