Systematic review and meta-analysis of the protective effect of resveratrol on multiple organ injury induced by sepsis in animal models

摘要

Sepsis may directly lead to multiple organ failure, which is among the leading causes of mortality in critically ill patients. According to data released by the Global Sepsis Alliance, the number of mortalities due to sepsis exceeded the combined number for prostate cancer, breast cancer and AIDS in 2012. To date, studies have reported that resveratrol has marked positive effects including anti-inflammatory, anti-oxidative and pro-microcirculatory functions in sepsis-induced organ injury, significantly improving the survival time and mortality of sepsis animals. The present systematic review sought to further clarify the efficacy and safety of resveratrol in the treatment of sepsis. Studies on resveratrol application in the treatment of sepsis-induced organ injury in animal models were reviewed by searching various Chinese and other language databases (PubMed, Embase, CNKI, WanFang and WeiPu) and by manually searching the references of related articles. The selection and evaluation of the studies was performed by two independent reviewers. A total of 260 related studies were initially identified. Following application of the exclusion factors and inclusion criteria, 11 studies were included. Meta-analysis revealed that resveratrol exerted significant protective effect in sepsis-induced animal models of organ injury, through anti-inflammatory, anti-oxidant and pro-microcirculatory functions compared with in the placebo group. While nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (NRF-2) are the two major signaling pathways to have been associated with the anti-inflammatory and anti-oxidative effects of resveratrol, these factors were not quantified for mean values, therefore not suitable for systematic evaluation. For related factors, the results of meta-analysis were as follows: For tumor necrosis factor-α (TNF-α), the standardized mean difference (SMD) was −13.50 [95% confidence interval (CI): −22.08, −4.91; P=0.002]; for malondialdehyde (MDA), the SMD was −3.10 (95% CI: −5.27, −0.93; P=0.005); for mean arterial pressure the SMD was 1.34 (95% CI: 0.07, 2.62; P=0.04); for interleukin (IL)-6 the SMD was −9.57 (95% CI: −20.90, 1.75; P=0.10); and for IL-10 the SMD was 0.80 (95% CI: −0.73, 2.34; P=0.31). It was concluded that resveratrol exerted significant anti-inflammatory and anti-oxidative effects through NF-κB and NRF-2 signaling pathways in animal models of sepsis-induced multiple organ injury, manifesting as significant downregulation of TNF-α and MDA expression and improved microcirculation, therefore ameliorating septic damage to the body, which may ultimately improve survival ratios.