PDF(Pubmed)
Abstract：
BACKGROUND: Autologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival.
METHODS: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells.
RESULTS: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors.
CONCLUSIONS: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.
METHODS: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells.
RESULTS: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors.
CONCLUSIONS: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.
摘要：
背景：自体脂肪移植受到无法预测的移植物存活的阻碍，这可能是由铁凋亡调节。谷胱甘肽(GSH),一种用于组织保存的强效抗氧化剂，具有铁凋亡调节活性；然而，其对脂肪移植物的影响尚不清楚。这项研究调查了GSH在脂肪移植物存活中的作用和机制。
方法:将人脂肪抽吸物皮下移植到生理盐水处理(对照)或GSH处理的裸鼠的背部。通过磁共振成像和组织学评估移植物存活。进行RNA测序以鉴定差异表达的基因和富集的途径。使用脂肪来源的干细胞的氧和葡萄糖剥夺(OGD)模型在体外评估GSH活性。
结果：与对照组相比，GSH诱导更好的结果，包括优越的移植物保留，外观,和组织学结构。RNA测序表明，在GSH处理的移植物中，铁凋亡的负调控增强，显示脂质过氧化物减少，更好的线粒体超微结构，和SLC7A11/GPX4轴激活。体外，GSH改善了OGD诱导的铁死亡，恢复细胞增殖，减少氧化应激，并上调铁中毒防御因子。
结论：我们的研究证实，铁凋亡参与调节脂肪移植物的存活，GSH通过抑制铁凋亡发挥保护作用。GSH辅助脂质转移是未来临床应用的有希望的治疗策略。
方法:将人脂肪抽吸物皮下移植到生理盐水处理(对照)或GSH处理的裸鼠的背部。通过磁共振成像和组织学评估移植物存活。进行RNA测序以鉴定差异表达的基因和富集的途径。使用脂肪来源的干细胞的氧和葡萄糖剥夺(OGD)模型在体外评估GSH活性。
结果：与对照组相比，GSH诱导更好的结果，包括优越的移植物保留，外观,和组织学结构。RNA测序表明，在GSH处理的移植物中，铁凋亡的负调控增强，显示脂质过氧化物减少，更好的线粒体超微结构，和SLC7A11/GPX4轴激活。体外，GSH改善了OGD诱导的铁死亡，恢复细胞增殖，减少氧化应激，并上调铁中毒防御因子。
结论：我们的研究证实，铁凋亡参与调节脂肪移植物的存活，GSH通过抑制铁凋亡发挥保护作用。GSH辅助脂质转移是未来临床应用的有希望的治疗策略。
