富血小板血浆治疗早发性卵巢功能不全的研究进展

doi:10.12280/gjfckx.20250022

摘要/Abstract

摘要：

早发性卵巢功能不全（premature ovarian insufficiency，POI）指育龄期女性过早出现卵巢功能衰退，可严重影响患者的生活质量和生育能力，其发病率呈逐年上升的趋势。目前以激素替代治疗（hormone replacement therapy，HRT）为主的传统治疗方式在一定程度上可以改善患者症状，但在恢复卵巢功能和实现生育方面效果有限。伴随再生医学的发展，富血小板血浆（platelet rich plasma，PRP）作为一种创新的生物学治疗再生策略，展示出促进组织修复和再生的巨大潜力。PRP富含多种生长因子，能够激活血管生成、细胞增殖、抗凋亡及细胞修复，为卵巢再生提供了可能性。目前的临床研究多为早期探索性试验，提示PRP可能改善卵巢微环境、激活卵泡发育、提高妊娠率，但由于样本量有限、缺乏大规模随机对照试验，相关证据仍需进一步验证。此外，PRP应用的安全性尚未完全明确，尽管目前尚未报道严重不良反应，但在其他领域存在感染、过敏等潜在风险。综述PRP在促进卵巢功能恢复中的潜在机制、临床应用现状及未来研究方向，旨在为临床治疗提供理论基础和研究方向。

关键词: 富血小板血浆, 再生, 治疗, 早发性卵巢功能不全, 生物学治疗

Abstract:

Premature ovarian insufficiency (POI), characterized by the premature decline of ovarian function in women of reproductive age, significantly impairs quality of life and fertility. Its incidence has been rising globally. While conventional hormone replacement therapy (HRT) alleviated symptoms, its efficacy in restoring ovarian function or achieving pregnancy remains limited. With the emergence of regenerative medicine, platelet rich plasma (PRP) has garnered attention as a novel biologic therapeutic strategy. PRP, enriched with diverse growth factors, demonstrates potential to activate angiogenesis, cell proliferation, anti-apoptosis, and cell repair, thereby offering a promising avenue for ovarian regeneration. Preliminary clinical studies, though predominantly exploratory, suggest that PRP may improve the ovarian microenvironment, reactivate folliculogenesis, and enhance pregnancy rates. However, current evidence is constrained by small sample sizes and a lack of large-scale randomized controlled trials. The safety profile of PRP remains incompletely defined. While no serious adverse effects have been reported in POI applications, risks (e.g. infection, hypersensitivity) observed in other medical fields warrant caution. This review synthesizes the potential mechanisms of PRP in ovarian functional recovery, summarizes current clinical progress, and identifies key research gaps, aiming to provide a theoretical basis and research directions for clinical treatment.

Key words: Platelet-rich plasma, Regeneration, Therapy, Premature ovarian insufficiency, Biological therapy

赵铭, 詹宏, 吴瑞瑾. 富血小板血浆治疗早发性卵巢功能不全的研究进展[J]. 国际妇产科学杂志, 2025, 52(4): 462-466.

ZHAO Ming, ZHAN Hong, WU Rui-jin. Research Advances in Platelet Rich Plasma Therapy for Premature Ovarian Insufficiency[J]. Journal of International Obstetrics and Gynecology, 2025, 52(4): 462-466.

图/表 2

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成分	作用机制	功能
PDGF^[14]	通过结合并激活2个结构相关的蛋白酪氨酸激酶受体（α受体和β受体）发挥其细胞效应；诱导肌动蛋白系统的重组并促使细胞沿着PDGF浓度梯度定向迁移；通过RAS-MAPK、PI3K和磷脂酶C-γ等信号通路发挥作用	促进血管生成；促进有丝分裂；活化巨噬细胞
TGF-β^[15-16]	是细胞生长和分化的关键调节蛋白，其中包括生长分化因子-9、骨形成蛋白-15，在早期卵泡发生和排卵中起重要作用；通过Smad2和Smad3发出信号，并转位到细胞核，调控靶基因的表达	促进组织再生愈合；调节炎症；诱导细胞增殖分化
VEGF^[17]	可作为颗粒细胞的生存因子；通过抑制胱天蛋白酶3的激活增强滤泡细胞的存活能力；通过激活PI3K/蛋白激酶B和丝裂原活化蛋白激酶激酶/ERK通路发挥作用	促进血管生成；抑制卵泡闭锁
EGF^[18]	是一种有效的上游功能因子；是CDC42的快速激活剂；通过提高CDC42-PI3K信号活性改善原始卵泡的瞬时激活；通过ERK1/2、PI3K等通路促进细胞减数分裂；通过MAPK和PI3K通路增强卵巢基质细胞的增殖	促进血管生成；促进细胞生成、增殖、分化
HGF^[19]	窦前卵泡抗细胞凋亡的关键调节因子；阻止可能导致卵泡闭锁的卵泡内类固醇的异常积累	促进血管生成；抑制细胞凋亡
FGF^[20]	是颗粒细胞内有效的有丝分裂因子，刺激颗粒细胞的DNA合成；通过抑制Hippo通路并上调活性Yes相关蛋白表达增强颗粒细胞的抗凋亡能力	促进血管生成；促进细胞增殖
IGF-1^[21]	调节颗粒细胞发育及功能的生长因子；以自分泌的形式刺激颗粒细胞的复制及分化	促进血管生成；抑制细胞凋亡；维持卵泡发育

成分	作用机制	功能
PDGF^[14]	通过结合并激活2个结构相关的蛋白酪氨酸激酶受体（α受体和β受体）发挥其细胞效应；诱导肌动蛋白系统的重组并促使细胞沿着PDGF浓度梯度定向迁移；通过RAS-MAPK、PI3K和磷脂酶C-γ等信号通路发挥作用	促进血管生成；促进有丝分裂；活化巨噬细胞
TGF-β^[15-16]	是细胞生长和分化的关键调节蛋白，其中包括生长分化因子-9、骨形成蛋白-15，在早期卵泡发生和排卵中起重要作用；通过Smad2和Smad3发出信号，并转位到细胞核，调控靶基因的表达	促进组织再生愈合；调节炎症；诱导细胞增殖分化
VEGF^[17]	可作为颗粒细胞的生存因子；通过抑制胱天蛋白酶3的激活增强滤泡细胞的存活能力；通过激活PI3K/蛋白激酶B和丝裂原活化蛋白激酶激酶/ERK通路发挥作用	促进血管生成；抑制卵泡闭锁
EGF^[18]	是一种有效的上游功能因子；是CDC42的快速激活剂；通过提高CDC42-PI3K信号活性改善原始卵泡的瞬时激活；通过ERK1/2、PI3K等通路促进细胞减数分裂；通过MAPK和PI3K通路增强卵巢基质细胞的增殖	促进血管生成；促进细胞生成、增殖、分化
HGF^[19]	窦前卵泡抗细胞凋亡的关键调节因子；阻止可能导致卵泡闭锁的卵泡内类固醇的异常积累	促进血管生成；抑制细胞凋亡
FGF^[20]	是颗粒细胞内有效的有丝分裂因子，刺激颗粒细胞的DNA合成；通过抑制Hippo通路并上调活性Yes相关蛋白表达增强颗粒细胞的抗凋亡能力	促进血管生成；促进细胞增殖
IGF-1^[21]	调节颗粒细胞发育及功能的生长因子；以自分泌的形式刺激颗粒细胞的复制及分化	促进血管生成；抑制细胞凋亡；维持卵泡发育

文献	组织类型	动物模型	干预措施	样本量（只）	研究结果
Shivaramu等^[25]	肝脏	大鼠	将大鼠随机分为空白对照组、干细胞组（5×10⁶）、0.5 mL PRP组、0.35 mg/kg HGF组、干细胞+PRP组、干细胞+HGF组、PRP+HGF组、干细胞+PRP+HGF组，每组20只	160	联合治疗比单独使用PRP或HGF显示出更好的护肝作用；干细胞、PRP和HGF对胆汁淤积诱导的肝纤维化具有协同改善及再生的作用
Marchante等^[26]	卵巢	小鼠	将8周龄年轻小鼠、28周龄中年小鼠和36周龄老年小鼠分别随机分为10 μL生理盐水空白组、10 μL PRP组和10 μL干细胞+PRP组，每组4只	36	PRP治疗激活卵泡的效率低于干细胞联合PRP治疗
Zhang等^[27]	骨关节	兔	将兔随机分为假手术组、0.3 mL生理盐水空白组、0.3 mL PRP组、0.3 mL干细胞组（1×10⁶/mL）、0.3 mL干细胞+PRP组，每组10只	50	PRP可增强干细胞的生物活性，包括增殖、迁移和黏附；联合治疗增强了软骨细胞的活性氧清除能力并抑制了细胞凋亡
Akbari等^[28]	神经	大鼠	将大鼠随机分为健康对照组、假手术组、PBS组、500 μL PRP组、干细胞组（1×10⁶）、干细胞+PRP组	58	联合治疗组在空间记忆改善方面表现更好；仅有联合治疗组恢复了基底突触传递

文献	组织类型	动物模型	干预措施	样本量（只）	研究结果
Shivaramu等^[25]	肝脏	大鼠	将大鼠随机分为空白对照组、干细胞组（5×10⁶）、0.5 mL PRP组、0.35 mg/kg HGF组、干细胞+PRP组、干细胞+HGF组、PRP+HGF组、干细胞+PRP+HGF组，每组20只	160	联合治疗比单独使用PRP或HGF显示出更好的护肝作用；干细胞、PRP和HGF对胆汁淤积诱导的肝纤维化具有协同改善及再生的作用
Marchante等^[26]	卵巢	小鼠	将8周龄年轻小鼠、28周龄中年小鼠和36周龄老年小鼠分别随机分为10 μL生理盐水空白组、10 μL PRP组和10 μL干细胞+PRP组，每组4只	36	PRP治疗激活卵泡的效率低于干细胞联合PRP治疗
Zhang等^[27]	骨关节	兔	将兔随机分为假手术组、0.3 mL生理盐水空白组、0.3 mL PRP组、0.3 mL干细胞组（1×10⁶/mL）、0.3 mL干细胞+PRP组，每组10只	50	PRP可增强干细胞的生物活性，包括增殖、迁移和黏附；联合治疗增强了软骨细胞的活性氧清除能力并抑制了细胞凋亡
Akbari等^[28]	神经	大鼠	将大鼠随机分为健康对照组、假手术组、PBS组、500 μL PRP组、干细胞组（1×10⁶）、干细胞+PRP组	58	联合治疗组在空间记忆改善方面表现更好；仅有联合治疗组恢复了基底突触传递