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姜黄素对紫杉醇诱导的大鼠脊髓和坐骨神经损伤的保护作用。

Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats.

机构信息

Department of Neurosurgery, Private Buhara Hospital, Erzurum, Turkey.

Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey.

出版信息

Neurochem Res. 2021 Feb;46(2):379-395. doi: 10.1007/s11064-020-03174-0. Epub 2020 Nov 17.

Abstract

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.

摘要

紫杉醇(PTX)是一种常用于治疗实体瘤的抗肿瘤药物,已知其会引起剂量限制的周围神经毒性。本研究旨在评估姜黄素(CUR)对大鼠紫杉醇诱导的脊髓和坐骨神经损伤的保护作用。大鼠腹腔内给予紫杉醇(2mg/kg,BW)连续 5 天,随后给予 CUR(100 和 200mg/kg,BW 每日在玉米油中)口服 10 天。我们的结果表明,CUR 显著降低了脊髓和坐骨神经中 NF-κB、TNF-α、IL-6、iNOS 和 GFAP 的 mRNA 表达水平,而增加了 Nrf2、HO-1 和 NQO1 的水平。此外,CUR 通过增加 Bcl-2 和 Bcl-xL,减少 p53、caspase-3、Apaf-1、LC3A、LC3B 和 beclin-1 的 mRNA 表达水平,抑制了凋亡和自噬途径的激活。结果表明,CUR 通过 LFB 染色和 H&E 染色也维持了脊髓和坐骨神经的组织学结构和完整性。CUR 给药后,紫杉醇诱导的脊髓组织中 8-OHdG、caspase-3 和 LC3B 的免疫组化表达降低。总之,我们的研究结果表明,CUR 对大鼠紫杉醇诱导的脊髓和坐骨神经损伤具有保护作用。

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