Use of dexmedetomidine to alleviate intestinal ischemia-reperfusion injury via intestinal microbiota modulation in mice

右美托咪啶通过调节小鼠肠道菌群减轻肠道缺血再灌注损伤

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作者:Ye-Hong Dong #, Jing-Juan Hu #, Fan Deng, Xiao-Dong Chen, Cai Li, Ke-Xuan Liu, Bing-Cheng Zhao

Background

Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota.

Conclusions

This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.

Methods

An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines.

Results

DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02±0.36 vs. normal saline (NS) + I/R 0.82±0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40±0.16 vs. 0.10±0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEX-pretreated mice decreased the release of inflammatory factors. Conclusions: This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.

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