Resveratrol抑制TNF-a诱导的Necroptosis在慢性创面治疗中的作用及其机制研究

Uncontrolled and excessive inflammation and continuous cell death play a crucial role in the cause of chronic non-healing wound even when there is no systemic infection. TNF-α is very important in chronic wound, but its regulatory mechanism and biological effect is still unclear. Our preliminary experiments found that: ⑴There is necroptosis induced by TNF-α in the chronic wound; ⑵ RSV can significantly suppress the mRNA level of TNF-a and restrain necroptosis in the chronic wound; ⑶ The suppression of TNF-α by RSV can be blocked by the special blocker of SIRT1. Based on these findings, we propose that RSV could accelerate the healing of chronic wounds through stimulating SIRT1 to suppress necroptosis induced by TNF-α. This study tends to explore the biological effect and signal mechanisms of RSV that cound suppress the excessive inflammatory response and inhibit the necroptosis in the chronic wound. It will provide new strategies and theoretical basis for both prevention and treatment of the chronic wound in clinical practice.

过度、失控的炎症反应和坏死持续存在是慢性创面难以愈合的重要原因。TNF-α在炎症反应、细胞坏死等病理过程中起着重要的调节作用，但其在慢性创面中的调控机制及生物学后果仍不清楚。程序性坏死necroptosis的发现使得对坏死进行调控成为可能。我们前期实验发现：⑴慢性创面组织存在程序性坏死necroptosis，且由TNF-α诱导产生；⑵白藜芦醇RSV治疗可有效抑制慢性创面组织中TNF-a的mRNA水平，并有效抑制necroptosis，⑶ RSV抑制TNF-α的作用可被SIRT1阻断剂所阻断。据此，我们提出：RSV通过激活SIRT1抑制TNF-α所诱导的necroptosis发生，从而促进慢性创面的愈合这一新机制。本研究拟从抑制持续存在的过度炎症反应，靶向拮抗necroptosis的全新角度，探明RSV治疗慢性创面的生物学作用及信号机制，为临床预防和治疗慢性创面提供新的策略和理论依据。