Yao Wanjun, Zhao Haiwen, Shi Ruoshi, Li Xiaohui, Li Yang, Ke Changbin, Liu Juying
Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Biochem Biophys Res Commun. 2017 May 13;486(4):1143-1148. doi: 10.1016/j.bbrc.2017.04.017. Epub 2017 Apr 6.
Bone cancer pain (BCP) is a serious chronic clinical condition and reactive oxygen species (ROS) were considered to be involved in its development and persistency. Normally, superoxide dismutase (SOD) converts superoxide anions to hydrogen peroxide (HO) and HO is then naturalized to be water by peroxiredoxin 4. We reported previously that recombinant protein transduction domain (PTD)-Cu/Zn SOD effectively scavenged excessive ROS and prevented cardiomyocytes from hypoxia-reoxygenation damage. However, whether PTD-Cu/Zn SOD would prevent BCP development is unknown. In the current study, we found that an implanted carcinoma in the rat tibia induced remarkable hyperalgesia, increased HO levels and decreased SOD and peroxiredoxin 4 levels. After administration of recombinant PTD-Cu/Zn SOD to these tumor-burden rats, their hyperalgesia was significantly attenuated and peroxiredoxin 4 expression was significantly increased. In addition, an increased expression of N-methyl-d-aspartic acid (NMDA) receptors and a decreased expression of γ-aminobutyric acid (GABA) receptors in this cancer pain were prevented by PTD-Cu/Zn SOD administration or peroxiredoxin 4 overexpression. Our data suggested that reactive oxygen species, at least in part, play a role in cancer metastatic pain development and persistency which can be attenuated by the adminstration of recombinant PTD-Cu/Zn SOD via the peroxiredoxin 4 modulation from oxidative stress.
骨癌疼痛（BCP）是一种严重的慢性临床病症，活性氧（ROS）被认为参与了其发生发展及持续过程。正常情况下，超氧化物歧化酶（SOD）将超氧阴离子转化为过氧化氢（HO），然后HO通过过氧化物酶4被还原为水。我们之前报道过重组蛋白转导结构域（PTD）-铜锌超氧化物歧化酶能有效清除过量的ROS，并防止心肌细胞发生缺氧复氧损伤。然而，PTD-铜锌超氧化物歧化酶是否能预防BCP的发生尚不清楚。在本研究中，我们发现大鼠胫骨植入癌可诱导显著的痛觉过敏，增加HO水平，降低SOD和过氧化物酶4水平。给这些荷瘤大鼠注射重组PTD-铜锌超氧化物歧化酶后，它们的痛觉过敏明显减轻，过氧化物酶4表达显著增加。此外，PTD-铜锌超氧化物歧化酶给药或过氧化物酶4过表达可预防这种癌痛中N-甲基-D-天冬氨酸（NMDA）受体表达增加和γ-氨基丁酸（GABA）受体表达减少。我们的数据表明，活性氧至少在一定程度上参与了癌转移疼痛的发生发展及持续过程，而通过过氧化物酶4调节氧化应激，注射重组PTD-铜锌超氧化物歧化酶可减轻这种疼痛。
