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富血小板血浆注射的全身效应。

The systemic effects of platelet-rich plasma injection.

机构信息

Department of Orthopaedic Surgery, Stanford University, California, USA.

出版信息

Am J Sports Med. 2013 Jan;41(1):186-93. doi: 10.1177/0363546512466383. Epub 2012 Dec 4.

DOI:10.1177/0363546512466383
PMID:23211708
Abstract

BACKGROUND

Platelet-rich plasma (PRP) is an autologous blood product used to treat acute and chronic tendon, ligament, and muscle injuries in over 86,000 athletes in the United States annually. The World Anti-Doping Agency (WADA) banned intramuscular PRP injections in competitive athletes in 2010 because of concerns that it may increase performance-enhancing growth factors. The ban on PRP was removed in 2011 because of limited evidence for a systemic ergogenic effect of PRP, but the growth factors within PRP remain prohibited.

PURPOSE

To quantify the effect of PRP injection on systemic growth factors with performance-enhancing effects and to identify molecular markers to detect treated athletes.

STUDY DESIGN

Descriptive laboratory study.

METHODS

Six ergogenic growth factors monitored by WADA-human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB)-were measured in 25 patients before (baseline) and at 0.25, 3, 24, 48, 72, and 96 hours after intratendinous leukocyte-rich PRP injection. Eating and exercise were prohibited for 3 hours before testing. Growth factors were quantified by enzyme-linked immunosorbent assay, and the change relative to each patient's baseline was calculated.

RESULTS

Relative to serum, PRP contained significantly more bFGF (226 vs 5 pg/mL), VEGF (1426 vs 236 pg/mL), and PDGF-BB (26,285 vs 392 pg/mL), but IGF-1 and hGH were not elevated. Serum levels increased significantly for IGF-1 at 24 and 48 hours, for bFGF at 72 and 96 hours, and for VEGF at 3, 24, 48, 72, and 96 hours after PRP injection. Additionally, VEGF was increased in all 25 patients after PRP treatment.

CONCLUSION

Serum IGF-1, VEGF, and bFGF levels are significantly elevated after PRP injection, supporting a possible ergogenic effect of PRP. An indirect marker for hGH doping, the product of IGFBP-3 × IGF-1, also significantly increased after PRP. Platelet-rich plasma appears to trigger an increase in circulating growth factors through activating biological pathways rather than by serving as a vehicle for the direct delivery of presynthesized growth factors. Elevated VEGF was observed in all patients after PRP, and ≥88% of patients had elevated VEGF at each time point from 3 to 96 hours after PRP, suggesting that VEGF may be a sensitive molecular marker to detect athletes recently treated with PRP.

CLINICAL RELEVANCE

This is the first and only adequately powered study of the systemic effects of PRP. We present evidence that PRP contains and may trigger systemic increases in substances currently banned in competitive athletes. Finally, we provide evidence that VEGF could serve as a useful molecular marker to detect athletes treated with PRP.

摘要

背景

富含血小板的血浆(PRP)是一种自体血液产品,每年在美国有超过 86000 名运动员用于治疗急性和慢性肌腱、韧带和肌肉损伤。世界反兴奋剂机构(WADA)在 2010 年禁止竞争性运动员肌肉内 PRP 注射,因为担心它可能会增加性能增强的生长因子。由于 PRP 对全身产生有益效果的有限证据,PRP 的禁令在 2011 年被取消,但 PRP 中的生长因子仍然被禁止。

目的

定量 PRP 注射对具有增强性能的全身生长因子的影响,并确定检测接受治疗的运动员的分子标记物。

研究设计

描述性实验室研究。

方法

在白细胞丰富的 PRP 内注射后 0.25、3、24、48、72 和 96 小时,测量 25 名患者(基线)之前和之后的六种与增强性能相关的生长因子(WADA-人生长激素(hGH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)、碱性成纤维细胞生长因子(bFGF 或 FGF-2)、血管内皮生长因子(VEGF)和血小板衍生生长因子-BB(PDGF-BB))。在测试前 3 小时禁止进食和运动。通过酶联免疫吸附试验定量生长因子,并计算每个患者相对于基线的变化。

结果

与血清相比,PRP 中 bFGF(226 对 5 pg/mL)、VEGF(1426 对 236 pg/mL)和 PDGF-BB(26285 对 392 pg/mL)含量明显更高,但 IGF-1 和 hGH 并未升高。PRP 注射后 24 和 48 小时 IGF-1 水平显著升高,72 和 96 小时 bFGF 水平升高,3、24、48、72 和 96 小时 VEGF 水平升高。此外,所有 25 名患者在接受 PRP 治疗后 VEGF 均升高。

结论

PRP 注射后血清 IGF-1、VEGF 和 bFGF 水平显著升高,支持 PRP 具有可能的增强性能效果。hGH 兴奋剂的间接标志物,IGFBP-3×IGF-1 的产物,在 PRP 后也显著增加。PRP 似乎通过激活生物途径而不是作为预先合成的生长因子的载体来引起循环生长因子的增加。在 PRP 治疗后,所有患者均观察到 VEGF 升高,并且在 PRP 后 3 至 96 小时的每个时间点,均有≥88%的患者 VEGF 升高,这表明 VEGF 可能是一种敏感的分子标志物,可用于检测最近接受 PRP 治疗的运动员。

临床相关性

这是第一项也是唯一一项充分研究 PRP 全身效应的研究。我们提供的证据表明,PRP 中含有并可能引发目前禁止竞争性运动员使用的全身物质增加。最后,我们提供的证据表明 VEGF 可作为检测接受 PRP 治疗的运动员的有用分子标志物。

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