Role of intestinal flora disturbance in development of POCD in aged mice: the relationship with Treg and Th1/Th2 cells in small intestine / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of intestinal flora disturbance in development of postoperative cognitive dysfunction (POCD) in aged mice and the relationship with regulatory T cells (Treg) and T helper cells 1/T helper cells 2 (Th1/Th2) in the small intestine.Methods Thirty-six SPF healthy male C57BL/6J mice,weighing 45-50 g,aged 18 months,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),POCD group and POCD plus VSL#3 group (group PV).POCD was induced by abdominal exploration.VSL#3 probiotics was given by intragastric gavage (300 μl per time,once a day) every 24 h for 7 consecutive days starting from the end of surgery in group PV.Morris water maze test was used to assess the cognitive function at day 7 after operation.Orbital venous blood samples were collected after the end of Morris water maze test,and animals were then sacrificed and small intestine and hippocampi were removed for measurement of the percentage of CD4+ CD25+ Foxp3+Treg,TCD4+IFN-γ+Th1 and CD4+IL-4+Th2 in the lamina propria of small intestine and plasma and expression of IL-4 and IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues,and IL-4 mRNA/IFN-γmRNA ratio was calculated.Results Compared with group C,the percentage of CD4+CD25+Foxp3+Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly decreased,the percentage of CD4+ IFN-γ+Th1 in the lamina propria of small intestine and plasma was increased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,the expression of IFN-γ mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was up-regulated,IL-4 mRNA/IFN-γ mRNA ratio was decreased,the escape latency and swimming distance were prolonged,and the time spent in the target quadrant was shortened in group POCD (P＜0.05).Compared with group POCD,the percentage of CD4+ CD25+ Foxp3+ Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly increased,the percentage of CD4+IFN-γ+Th1 in the lamina propria of small intestine and plasma was decreased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was upregulated,the expression of IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,IL-4 mRNA/IFN-γmRNA ratio was increased,the escape latency and swimming distance were shortened,and the time spent in the target quadrant was prolonged in group PV (P＜ 0.05).Conclusion Intestinal flora disturbance can promote the development of POCD in aged mice,which is related to the decreased percentage of Treg and Th1/Th2 imbalance in the small intestine.