Yoshida Mamoru, Funasaki Hiroki, Kubota Makoto, Marumo Keishi
Department of Orthopaedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan,
J Orthop Sci. 2015 Jan;20(1):186-95. doi: 10.1007/s00776-014-0650-z. Epub 2014 Sep 25.
Tendinopathy is the most common tendon disorder. The etiology is still uncertain, and the disorder poses many therapeutic problems. In a few clinical studies, analgesic effects of high molecular weight hyaluronan (HMW HA) injections were observed, but the underlying mechanisms were not elucidated. In the present study, we analyzed the therapeutic effects of hyaluronan injections for tendinopathy in an animal model.
We made the tendinopathy rat model using a rodent treadmill machine. Rats with tendinopathy were injected with HMW HA (HA group), normal saline (NS group), or nothing (control group) into the space between the patellar tendon and the fat pad bilaterally, or were injected with HMW HA into the right knees and with saline to the left knees (HA/NS group), 5 times every 4 days. To assess the pain-relieving effect of HA, the spontaneous locomotor activities at night (12 h) and weight bearing of hind paws were measured every day. Histological sections of the patellar tendon stained with hematoxylin-eosin or prepared by TdT-mediated dUTP nick end labeling were microscopically analyzed.
The number of spontaneous locomotor activities in the HA group was significantly larger than those in NS or control groups, and in the HA group they recovered up to a healthy level. The percent weight distribution of the right hind paws was significantly increased along with the number of injections. On histologic examinations, the numbers of microtears, laminations, or apoptotic cells in the patellar tendons in the HA group were significantly lower than those in the NS or the control groups.
The injections of HMW HA were effective for pain relief and for partial restoration of the patellar tendon in our tendinopathy rat model, and thus may become an effective therapeutic modality for the disease.
肌腱病是最常见的肌腱疾病。其病因仍不明确，该疾病带来了许多治疗难题。在一些临床研究中，观察到了高分子量透明质酸（HMW HA）注射的镇痛效果，但潜在机制尚未阐明。在本研究中，我们在动物模型中分析了透明质酸注射对肌腱病的治疗效果。
我们使用啮齿动物跑步机制作肌腱病大鼠模型。将肌腱病大鼠双侧髌腱与脂肪垫之间的间隙注射HMW HA（HA组）、生理盐水（NS组）或不注射（对照组），或者右膝注射HMW HA，左膝注射生理盐水（HA/NS组），每4天注射5次。为评估HA的止痛效果，每天测量夜间（12小时）的自发运动活动和后爪负重。对苏木精-伊红染色或经TdT介导的dUTP缺口末端标记制备的髌腱组织切片进行显微镜分析。
HA组的自发运动活动次数显著多于NS组或对照组，且HA组的活动次数恢复到了健康水平。随着注射次数的增加，右后爪的重量分布百分比显著增加。组织学检查显示，HA组髌腱中的微撕裂、分层或凋亡细胞数量显著低于NS组或对照组。
在我们的肌腱病大鼠模型中，注射HMW HA对缓解疼痛和髌腱的部分恢复有效，因此可能成为该疾病的一种有效治疗方式。
