Propofol ameliorated diabetic peripheral neuropathic pain via modulating miR-150/EPHB2 axis
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ORIGINAL ARTICLE
Propofol ameliorated diabetic peripheral neuropathic pain via modulating miR‑150/EPHB2 axis Dongyi Fan1 · Simin Yang1 · Jingyu Yao1 · Yuxiang Han1 · Lukun Yang1 Accepted: 31 August 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020
Abstract Background Diabetic peripheral neuropathic pain (DPNP) is a kind of common diabetic chronic complications and affects life quality of patients. Given the protective function of propofol in multiple diseases, the aim of this study is to investigate the mechanism of propofol in DPNP. Methods The streptozocin (STZ)-induced DPNP rat models were established for in vivo study and the high glucose (HG)induced astrocytes were used for in vitro study, which was isolated from spinal cord of control rats. The paw withdraw thermal latency and mechanical withdrawal threshold were measured. The expression of pro-inflammatory cytokines containing tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) was determined by qRT-PCR assay. The interaction between miR-150 and EPBH2 was detected by luciferase activity assay. Results We demonstrated that propofol alleviated the STZ-induced DPNP in vivo. More importantly, propofol was proven to inhibit pro-inflammatory cytokine in DPNP rats, including TNF-α, IL-1β, and IL-6. Similarly, propofol suppressed HGinduced pro-inflammatory cytokine in astrocytes. Mechanically, propofol enhanced miR-150 expression in vivo and in vitro; furthermore, EPHB2 was confirmed as a direct target of miR-150 and was modulated by miR-150. In rescue experiments, propofol alleviated the impact of HG treatment via up-regulating miR-150 expression. Conclusion These findings concluded that propofol could inhibit pro-inflammatory cytokine expression and promote the activation of astrocytes, and then ameliorated DPNP by modulating miR-150/EPHB2 axis in vivo and in vitro, which might provide a potential clinic strategy for DPNP treatment. Keywords Propofol · Diabetic peripheral neuropathic pain · miR-150 · EPHB2
Introduction Diabetic peripheral neuropathic pain (DPNP) is a kind of common diabetic chronic complications, resulting in diabetic patients with acute or chronic pain syndrome (Davies et al. 2006). Diabetic patients occasionally suffer from severe hyperalgesia and allodynia (Didangelos et al. 2014). Moreover, DPNP is a typical chronic neurogenic pain, which is difficult to treat and greatly affects the physiological function and life quality of patients. Meanwhile, it brings heavy burden to individuals and society (Boulton et al. 2004). The pathogenesis of DPNP is complex, including inflammation, * Lukun Yang [email protected] 1
Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Xiangzhou District, Zhuhai 519000, Guangdong, China
repair process, structure, and gene expression, indicating that DPNP is a combination of multiple factors (Vanotti 2007). Propofol is a common anesthetic and used in surgery operation. While it acts as an anest
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