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载超氧化物歧化酶的生物可降解纳米颗粒靶向卵泡刺激素肽可保护支持细胞免受氧化应激。

Superoxide dismutase-loaded biodegradable nanoparticles targeted with a follicle-stimulating hormone peptide protect Sertoli cells from oxidative stress.

机构信息

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.

出版信息

Fertil Steril. 2014 Feb;101(2):560-7. doi: 10.1016/j.fertnstert.2013.10.034. Epub 2013 Nov 26.

Abstract

OBJECTIVE

To evaluate targeted superoxide dismutase (SOD)-loaded biodegradable nanoparticles' (NPs) ability to protect Sertoli cells from hydrogen peroxide (H2O2)-induced oxidative stress.

DESIGN

Cell culture controlled experimental study.

SETTING

Research laboratory.

CELLS

Mouse testis Sertoli cells (TM4).

INTERVENTIONS

Sertoli cells were exposed to 0-200 μg/mL plain media, unconjugated NPs, or FSH peptide-conjugated NPs for 2 or 24 hours to assess uptake. Next, Sertoli cells were exposed to 0-50 mmol H₂O₂ with 0-1 mg/mL unconjugated SOD-loaded NPs, FSH-conjugated SOD-loaded NPs, or equivalent units of SOD in solution as a control for 2-6 hours to assess influence on cell survival after oxidative stress.

MAIN OUTCOME MEASURE(S): Cell viability, flow cytometry, and microscopy.

RESULT(S): FSH peptide targeting improved uptake of NPs by Sertoli cells. FSH-conjugated SOD-NPs significantly protected Sertoli cells at 6 hours of H₂O₂--induced oxidative stress, with 100% survival with FSH-conjugated SOD-NPs compared with unconjugated SOD-NPs (45%) or SOD in solution (36%).

CONCLUSION(S): Conjugation of NPs with FSH peptide improves cellular uptake and survival when SOD-loaded NPs are coincubated with Sertoli cells undergoing oxidative stress. This study represents a step toward developing NPs for the targeted treatment of testicular oxidative stress.

摘要

目的

评估靶向超氧化物歧化酶(SOD)负载的可生物降解纳米颗粒(NPs)保护睾丸支持细胞免受过氧化氢(H2O2)诱导的氧化应激的能力。

设计

细胞培养对照实验研究。

设置

研究实验室。

细胞

小鼠睾丸支持细胞(TM4)。

干预

支持细胞暴露于 0-200μg/ml 普通培养基、未结合 NPs 或 FSH 肽结合 NPs 2 或 24 小时以评估摄取。接下来,支持细胞暴露于 0-50mmol H₂O₂,同时暴露于 0-1mg/ml 未结合 SOD 负载 NPs、FSH 结合 SOD 负载 NPs 或溶液中相当数量的 SOD 作为氧化应激后细胞存活的对照 2-6 小时。

主要观察指标

细胞活力、流式细胞术和显微镜。

结果

FSH 肽靶向提高了 NPs 对支持细胞的摄取。FSH 结合 SOD-NPs 在 6 小时 H₂O₂诱导的氧化应激下显著保护支持细胞,与未结合 SOD-NPs(45%)或溶液中 SOD(36%)相比,FSH 结合 SOD-NPs 组具有 100%的存活率。

结论

FSH 肽与 NPs 的缀合可提高细胞摄取率,并在 SOD 负载 NPs 与发生氧化应激的支持细胞共孵育时提高存活率。该研究为开发靶向治疗睾丸氧化应激的 NPs 迈出了一步。

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