Propofol ameliorated diabetic peripheral neuropathic pain via modulating miR-150/EPHB2 axis

Abstract

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. 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. 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 HG-induced 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. 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.