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首页> 外文期刊>Drug Design, Development and Therapy >Ulinastatin Promotes Regeneration of Peripheral Nerves After Sciatic Nerve Injury by Targeting let-7 microRNAs and Enhancing NGF Expression
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Ulinastatin Promotes Regeneration of Peripheral Nerves After Sciatic Nerve Injury by Targeting let-7 microRNAs and Enhancing NGF Expression

机译：通过靶向Let-7 MicroRNA和增强NGF表达，乌纳替肽促进坐骨神经损伤后周围神经的再生

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Background: Peripheral nerve injury is characterized as a common clinical problem. Ulinastatin (UTI) is a serine protease inhibitor with many biological activities including anti-inflammatory and antioxidant effects. Nonetheless, it is unknown whether UTI has a protective effect on peripheral nerve injury. Methods: Thirty rats were divided into the sham operation group, the sciatic nerve injury group (injected with normal saline), and the UTI treatment group (80mg/kg/day for two consecutive weeks). Sciatic nerve function index (SFI) was used to assess the biological functions of the sciatic nerve, and compound muscle action potential (CMAP) was measured by electrophysiology. The expressions of let-7 miRNA members were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Nerve growth factor (NGF), nerve regeneration-related proteins GAP43 and NF200, and myelin formation-related proteins MAG and PMP22 expressions were explored by Western blot. After Schwann cells were transfected with let-7 mimics, pcDNA3.1-NGF, let-7 inhibitors, NGF siRNA and their corresponding controls, 5-ethynyl-2?-deoxyuridine (EdU) assay, and Transwell assays were employed to investigate the proliferation and migration of Schwann cells. Hsub2/subOsub2/sub was utilized to construct oxidative injury to cells, and the contents of MDA, SOD, GSH, and CAT were determined. Results: UTI treatment remarkably increased SFI of the rats and CMAP of sciatic nerve, enhanced nerve regeneration, and myelin regeneration, and raised the production of GAP43, NF200, MAG, and PMP22. Furthermore, it was found that UTI markedly reduced let-7 miRNAs’ expressions and increased NGF expression after sciatic nerve injury. The dual-luciferase reporter assay validated that let-7 miRNAs targeted NGF, and functional experiments demonstrated that low expression of let-7 miRNAs and NGF overexpression contributed to Schwann cells’ proliferation and migration. Additionally, UTI treatment repressed the oxidative stress regulated by let-7/NGF axis. Conclusion: UTI modulates the let-7/NGF axis to inhibit oxidative stress, promote nerve regeneration, and facilitate function recovery after peripheral nerve injury.
机译：背景：周围神经损伤的特征是常见的临床问题。 UlinaTatin（UTI）是一种丝氨酸蛋白酶抑制剂，具有许多生物活性，包括抗炎和抗氧化作用。尽管如此，uti是否对周围神经损伤具有保护作用。方法：将30只大鼠分为假手术组，坐骨神经损伤组（注射甘氨酸），uti治疗组（连续两周80mg / kg /天）。使用坐骨神经函数指数（SFI）来评估坐骨神经的生物学功能，通过电生理学测量复合肌动作电位（CMAP）。通过定量的实时聚合酶链反应（QRT-PCR）检测Let-7 miRNA成员的表达。通过Western印迹探讨了神经生长因子（NGF），神经再生相关蛋白质GAP43和NF200和髓鞘形成相关蛋白质MAG和PMP22表达。用Let-7模拟物转染Schwann细胞后，使用PCDNA3.1-NGF，Let-7抑制剂，NGF siRNA及其相应的对照，使用5-炔基-2→-deoxyuridine（EDU）测定和Transwell测定来研究Schwann细胞的增殖和迁移。 H 2 O 2 用于构建细胞氧化损伤，并确定MDA，SOD，GSH和猫的含量。结果：UTI治疗显着增加了坐骨神经，增强神经再生和髓鞘再生的大鼠和CMAP的SFI，并提高了GAP43，NF200，MAG和PMP22的生产。此外，发现UTI显着降低了Let-7 miRNA的表达和坐骨神经损伤后的NGF表达增加。双荧光素酶报告器测定验证了Let-7 miRNA靶向NGF，并且功能实验表明，Let-7 miRNA和NGF过表达的低表达导致施旺细胞的增殖和迁移有助于。另外，UTI处理压抑了由Let-7 / NGF轴调节的氧化应激。结论：UTI调节Let-7 / NGF轴以抑制氧化应激，促进神经再生，并促进周围神经损伤后的功能恢复。

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