Role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice / 中华麻醉学杂志

ABSTRACT

Objective@#To evaluate the role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice.@*Methods@#Sixty SPF healthy male C57BL/6J mice, aged 18 months, were divided into 4 groups (n=15 each) by a random number table method: control group (group C), operation group (group O), operation plus lactobacillus rhamnosus group (group OL) and operation plus fecal microbiota transplantation group (group OF). Exploratory laparotomy was performed in O, OL and OF groups.In group PL, lactobacillus rhamnosus 200 μl (1×109 CFU/ml, 200 μl/day) was given by gavage once a day for 10 days starting from the end of surgery, and mice received about 0.2×109 CFU probiotics per day.In group OF, broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L, vancomycin 500 mg/L, ciprofloxacin 200 mg/L, imipenem cilastatin 250 mg/L and metronidazole 1 g/L) was added to the drinking water at 7 weeks prior to operation and replaced with sterile tap water at 72 h before operation, and fecal filtrates 200 μl was given by gavage once a day for 10 days starting the end of operation.Five mice were sacrificed at day 10 after operation in each group, and Evans blue extravasation test was used to measure the vascular permeability of jejunum and ileum.Five mice were sacrificed at day 10 after operation in each group, and the small intestinal and hippocampal tissues and orbital venous blood samples were obtained for determination of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), IL-4 and IL-10 levels by enzyme-linked immunosorbent assay.Five mice were selected at day 10 after operation in each group, and the Morris water maze test was used to assess the cognitive function.@*Results@#Compared with group C, the vascular permeability of jejunum and ileum was significantly increased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were increased, the levels of IL-4 and IL-10 were decreased, the swimming distance and escape latency were prolonged, and the time spent in the target quadrant was shortened in group O (P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in OL and OF groups (P>0.05). Compared with group O, the vascular permeability of jejunum and ileum was significantly decreased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were decreased, the levels of IL-4 and IL-10 were increased, the swimming distance and escape latency were shortened, and the time spent in the target quadrant was prolonged in OL and OF groups (P<0.05).@*Conclusion@#Intestinal flora disturbance can mediate inflammatory responses in the hippocampus and cause perioperative neurocognitive disorders in aged mice.