McCarty William J, Cheng Justin C, Hansen Bradley C, Yamaguchi Tomonori, Firestein Gary S, Masuda Koichi, Sah Robert L
University of California at San Diego, La Jolla, CA 92093-0412, USA.
Arthritis Rheum. 2012 Dec;64(12):3993-4003. doi: 10.1002/art.37682.
The residence time of hyaluronan (HA) in knee joint synovial fluid (SF) was investigated using a rabbit anterior cruciate ligament transection (ACLT) model. The aims of this study were to assess, at 7 and 28 days after surgery, the 1) HA concentration and molecular mass (M(r) ) distribution in the SF, 2) endogenous replenishment of HA after saline washout, 3) HA residence times in the SF, and 4) synovium and subsynovium cellularity of the knee joints of rabbits subjected to ACLT, compared to sham-operated and nonoperated control joints.
Adult NZW rabbits underwent ACLT or sham surgery on one hind limb, while each contralateral limb was the nonoperated control. On day 7 or 28 after surgery, the joints were aspirated for SF, lavaged with saline, and injected with saline or polydisperse HA, and samples were obtained for analysis at set time points up to 8 hours after injection. Joint fluid samples were analyzed for the concentration and M(r) distribution of HA to calculate the HA residence time constant.
Analysis of HA concentrations and M(r) distributions showed 1) loss of high-M(r) HA in the SF on day 7 and a shift toward a lower-M(r) distribution on day 28, 2) endogenous replenishment of high-M(r) HA after washout, and 3) M(r) -dependent loss of HA from the knee joints after ACLT, particularly on day 7 postsurgery. The HA residence time decreased with decreasing HA M(r) (residence time ∼27 hours with an M(r) load of 7,000-2,500 kd, to ∼7 hours with an M(r) load of 250-50 kd). HA residence time also decreased (by ∼70%) in the knee joints on day 7 after ACLT. The subsynovium of the joints subjected to ACLT displayed increased cellularity and neovascularization on days 7 and 28 postsurgery.
The residence time of HA in the SF is transiently decreased after ACLT, suggesting that a biophysical transport mechanism is responsible for the altered composition of the SF after joint injury or during inflammation.
采用兔前交叉韧带切断术（ACLT）模型研究透明质酸（HA）在膝关节滑液（SF）中的停留时间。本研究的目的是在术后7天和28天评估：1）滑液中HA的浓度和分子量（M(r)）分布；2）生理盐水冲洗后HA的内源性补充；3）HA在滑液中的停留时间；4）与假手术和未手术的对照关节相比，接受ACLT的兔膝关节滑膜和滑膜下层的细胞密度。
成年新西兰白兔一侧后肢接受ACLT或假手术，对侧后肢作为未手术对照。术后第7天或第28天，抽取关节滑液，用生理盐水冲洗，然后注射生理盐水或多分散HA，并在注射后长达8小时的设定时间点采集样本进行分析。分析关节液样本中HA的浓度和M(r)分布，以计算HA停留时间常数。
对HA浓度和M(r)分布的分析显示：1）术后第7天滑液中高M(r) HA减少，第28天向低M(r)分布转变；2）冲洗后高M(r) HA有内源性补充；3）ACLT后膝关节中HA因M(r)不同而流失，尤其是术后第7天。HA停留时间随HA M(r)降低而减少（M(r)负荷为7,000 - 2,500 kd时停留时间约为27小时，M(r)负荷为250 - 50 kd时约为7小时）。ACLT术后第7天膝关节中HA停留时间也减少（约70%）。ACLT关节的滑膜下层在术后第7天和第28天细胞密度增加且有新生血管形成。
ACLT后HA在滑液中的停留时间短暂减少，提示生物物理转运机制导致关节损伤或炎症期间滑液成分改变。
