白藜芦醇对于小鼠败血症休克的保护作用及其作用机制的研究

Protective effects of resveratrol on sepsis and its involved mechanisms

目的从动物休克模型和细胞水平上研究白藜芦醇(resveratrol,Res)对败血症的调节作用及其分子药理学作用机制。方法通过建立小鼠盲肠结扎穿孔诱导的败血症休克模型(CLP),研究白藜芦醇给药后的小鼠的存活率。然后利用体外培养的心肌细胞建立LPS损伤模型,采用反转录PCR(RT-PCR)、Real-time PCR检测细胞内源性TNF-α、SIRT1等的mRNA的表达水平,Western blot分析NF-κB重要亚基的蛋白表达水平。结果与单纯休克模型组相比较,腹腔注射白藜芦醇(1和5 mg·kg-1·d-1)治疗明显增加败血症休克小鼠的存活率;白藜芦醇处理明显促进SIRT1、SIRT6和SIRT7的mRNA表达,抑制LPS诱导的NF-κB核转位。结论适当剂量的白藜芦醇可能通过上调SIRT家族成员,并抑制NF-κB炎症反应通路,对败血症休克具有潜在的药理学保护作用。

Aim To investigate the effect of resveratrol（ Res） on septic mice and LPS-insulted H9c2 cells,as well as its involved mechanisms. Methods By use of a mouse cecal ligation and puncture-induced septic model（ CLP）,the survival of septic mice was evaluated after resveratrol treatments. H9c2 cells were insulted by LPS and then treated with resveratrol,the mRNA expressions of TNF-α,SIRT1 and other class III HDAC members were detected using RT-PCR and realtime PCR,Finally,the protein levels of nuclear p65,an important subunit of NF-κB, were measured in H9c2 cells using Western blot assay,to reveal the effect of resveratrol on LPS-induced nuclear translocation of NF-κB. Results Compared with the control septic animals,intraperitoneal injection of resveratrol（ 1 or 5 mg·kg- 1·d- 1） significantly increased the survival of septic mice. Furthermore,resveratrol significantly increased mRNA expressions of SIRT1,SIRT2,SIRT6 and SIRT7 in LPS-insulted H9c2 cells. Resveratrol also remarkably inhibited LPS-induced nuclear translocation of NF-κB. Conclusion An appropriate dose of resveratrol protects septic mouse hearts from the injury induced by LPS through the activation of SIRT family members and the inhibition of NF-κB pathway.