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 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.

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.

中文翻译：

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丙泊酚通过调节miR-150 / EPHB2轴改善了糖尿病周围神经性疼痛

背景

糖尿病周围神经性疼痛（DPNP）是一种常见的糖尿病慢性并发症，影响患者的生活质量。鉴于丙泊酚在多种疾病中的保护功能，本研究的目的是研究丙泊酚在DPNP中的作用机理。

方法

建立了链脲佐菌素（STZ）诱导的DPNP大鼠模型用于体内研究，高糖（HG）诱导的星形胶质细胞用于体外研究，该模型是从对照组大鼠的脊髓中分离得到的。测量爪的退缩热潜伏期和机械退缩阈值。通过qRT-PCR测定确定包含肿瘤坏死因子（TNF）-α，白介素-1β（IL-1β）和白介素-6（IL-6）的促炎细胞因子的表达。通过荧光素酶活性测定来检测miR-150和EPBH2之间的相互作用。

结果

我们证明了异丙酚在体内减轻了STZ诱导的DPNP。更重要的是，已证明丙泊酚可抑制DPNP大鼠的促炎细胞因子，包括TNF-α，IL-1β和IL-6。同样，异丙酚可抑制星形胶质细胞中HG诱导的促炎细胞因子。机械上，异丙酚在体内和体外增强miR-150的表达；此外，EPHB2被确认为miR-150的直接靶标，并被miR-150调节。在救援实验中，丙泊酚通过上调miR-150表达减轻了HG治疗的影响。

结论

这些发现表明，异丙酚可以抑制促炎细胞因子的表达并促进星形胶质细胞的活化，然后通过在体内外调节miR-150 / EPHB2轴来改善DPNP，这可能为DPNP治疗提供了潜在的临床策略。