Nrf2/HO-1-sulfiredoxin1 pathway involved in nanobubble hydrogen-dissolved water-mediated protective effects by ultrasound-guided early local injection in a rat model of chronic constriction injury-induced neuropathic pain

在慢性束缚损伤诱导的神经性疼痛大鼠模型中,超声引导下早期局部注射纳米气泡氢溶解水介导的保护作用涉及Nrf2/HO-1-硫氧还蛋白1通路。

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Abstract

INTRODUCTION: Neuropathic pain (NP) is a kind of common and intractable chronic pain. Hydrogen (H(2))-rich water exhibited protective effects in NP by intrathecal injection, drinking, and intraperitoneal injection. The nanobubble H2-dissolved water (NHW) is a solution that contains H(2) bubbles and H(2) in lysis state. Therefore, this study aimed to observe the effects of ultrasound-guided local injection with NHW in the model of NP, and try to find its possible mechanism. METHODS: The rat sciatic nerve was ligated to establish chronic constriction injury (CCI)-induced NP model. The CCI rats received NHW at low or high concentrations 1 or 3 times (n = 6). During the experiment, the paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL) were detected. At 14 days after CCI, the organizational structure of nerve, inflammatory response, and oxidative stress damage were measured. Additionally, the Nrf2/HO-1 and sulfiredoxin-1 were also detected by western blotting and RT-PCR. RESULTS: Compared with low concentration, in the high concentration group, the PWT and PWL were attenuated on Day 1, 3, 5, 7, and 14 after CCI (p < 0.05). On Day 14, nerve injury, inflammatory response, and oxidative stress injury were relieved significantly in high concentration than at low concentration, and the effect was greater at multiple doses (3 times) at high concentrations (p < 0.05), as were the increase in the protein and mRNA levels of Nrf2/HO-1 and sulfiredoxin-1. CONCLUSION: Ultrasound-guided early local injection of NHW attenuated sciatic nerve injury, alleviated mechanical allodynia and thermal hyperalgesia and inhibited inflammation and oxidative stress damage via the Nrf2/HO-1-sulfiredoxin1 pathway in a rat model of CCI.

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