Effect of Dexmedetomidine on Intestinal Barrier Function and Intestinal Microbiota in Laparoscopic Pneumoperitoneum Rats
[Objective]The purpose of this study was to investigate the effects of dexmedetomidine(DEX)on intestinal barrier function and intestinal microbiota in rats undergoing laparoscopic pneumoperitoneum.[Method]Thirty SD rats were randomly divided into three groups:Sham group(n=6),CO2 pneumoperitoneum group(CO2)(n=12)and DEX group(n=12).The rats in CO2 and DEX groups were intraperitoneally injected with 1 mL/kg normal saline and 50 μg/kg DEX 30 min before pneumoperitoneum,respectively,and then maintained at 15 mmHg pneumoperitoneum pressure for 90 min to establish an pneumoperitoneum model.Pneumoperitoneum was impassable in Sham group,and other operations were the same as those in CO2 group.The ileum tissues were collected 12 and 24 h after pneumoperitoneum,and the histopathologic changes were observed.The contents of malondialdehyde(MDA),glutathione(GSH),interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)activity of ileum in rats were determined by the kit.The mRNA relative expression of occlusive zonal-1(ZO-1),occlusive protein-1(Claudin-1)and occlusive protein(Occludin)was detected by Real-time quantitative PCR.The contents of ileal tissue were collected and the changes of ileal microflora were detected by high-throughput paired-end sequencing.[Result]Compared with Sham group,the structure of ileum was disordered,intestinal villi deformed and inflammatory cell infiltrated in CO2 group.MDA,IL-6,IL-1β and TNF-α contents,and MPO activity were extremely significantly increased(P＜0.01),GSH content and mRNA expression of ZO-1,Occludin,Claudin-1 genes were extremely significantly decreased(P＜0.01).The diversity of intestinal flora decreased.At the phylum level,the relative abundance of Firmicutes showed a decreasing trend(P＞0.05),while the relative abundance of Actinobacteria and Proteobacteria showed an increasing trend(P＞0.05).At the genus level,the relative abundance of Lactobacillus and Allobaculum showed a decreasing trend(P＞0.05),while the relative abundance of Bifidobacterium showed an increasing trend(P＞0.05).Compared with CO2 group,the ileal tissue structure disorder and intestinal villi deformation of rats in DEX group were relieved,and inflammatory cell infiltration was reduced.GSH content and mRNA expression of ZO-1,Claudin-1 and Occludin genes were extremely significantly or significantly increased(P＜0.01 or P＜0.05),MDA,IL-6,IL-1β and TNF-α contents,and MPO activity were significantly or extremely significantly decreased(P＜0.05 or P＜0.01).The diversity of intestinal flora increased.At the phylum level,the relative abundance of Firmicutes showed an increasing trend(P＞0.05),while the relative abundance of Actinobacteria and Proteobacteria showed a decreasing trend(P＞0.05).At the genus level,the abundance of Lactobacillus showed an increasing trend(P＞0.05),while the abundance of Bifidobacterium and Allobaculum showed a decreasing trend(P＞0.05).[Conclusion]DEX could increase the abundance and diversity of intestinal microbiota by improving oxidative stress,the release of inflammatory factors,and the structure of intestinal flora,so as to alleviate intestinal damage caused by laparoscopic pneumoperitoneum.
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