[Animal experiment]-The role of intestinal flora disturbance in perioperative neurocognitive impairment in aged mice

  Perioperative neurocognitive disorder (PND) is a change in mental activity, personality, social skills, and cognitive ability of patients after anesthesia or surgery, which is common in elderly patients. Clarifying its pathophysiological mechanism helps to formulate effective preventive measures, and the diversity and stability of the gut flora in elderly patients is significantly reduced. And surgery, especially gastrointestinal surgery, exacerbated the imbalance of intestinal flora. In recent studies, the "gut-brain dialogue" mediated by the "gut flora-gut-brain axis" serves as a two-way communication between the gut flora and the immune-mediated brain. Nervous system diseases (such as Guillain Valley syndrome, multiple sclerosis, and neuromyelitis optica) and non-immune-mediated central nervous system diseases (such as depression, anxiety, and autism) play an important role.

  In order to evaluate the role of intestinal flora imbalance in the perioperative neurocognitive dysfunction in elderly mice, Wang Guangji, Wu Xiaoe, Han Shouyin and other 60 SPF healthy male C57BL/6J mice, 18 months old, from the People’s Hospital of Zhongzhou University , Divided into 4 groups according to random number representation (n = 15): control group (C group), surgery group (O group), surgery + lactobacillus group (OL group) and surgery + fecal bacterial transplantation group (OF group) . The O, OL and OF groups underwent exploratory abdominal surgery. In the PL group, 200 μl of Lactobacillus rhamnosus was intragastrically administered once a day for 10 consecutive days after surgery, and the mice were able to obtain approximately 0.2×109 CFU of probiotics per day. Seven weeks before the OF group, a broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L, vancomycin 500 mg/L, ciprofloxacin 200 mg/L, imipenem and cilastatin 250 mg/L metronidazole 1 g/L) was added to the drinking water of mice. In addition, use sterile tap water 72 hours before surgery. After the operation, 200μl of fecal bacterial filtrate was administered into the stomach once a day for 10 days. On the 10th day after the operation, 5 mice in each group were sacrificed, and the Evans blue leak test was used to detect air transmission and ileal vascular permeability. On the 10th day after the operation, 5 mice in each group were sacrificed, the small intestine, hippocampus tissue and orbital venous blood were collected, and IL-6, IL-17, TNF-α, IFN-γ, IL- were detected in Figure 4. IL-. 10 levels. Ten days after the operation, five mice were taken from each group, and the Morris water maze test was used to determine the cognitive function of the mice. The results showed that compared with the C group, the air and ileum vascular permeability of the O group increased, and the levels of IL-6, IL-17, TNF-α, and IFN-γ in the small intestine, peripheral blood and hippocampus increased. O group increased, IL-4 level and IL-10 decreased, swimming distance and escape latency were prolonged, and the time in the subject quadrant was shortened (P0.05); in contrast, air and ileal permeability decreased in OL and OF groups , The levels of small intestine and peripheral blood decreased, and hippocampal IL-6, IL-17, TNF-α and IFN-γ decreased. IL-4 and IL-10 levels increased, the swimming distance and escape diving time were shortened, and the stay time in the target quadrant was extended (P\u003c0.05). Imbalance of intestinal flora mediates hippocampal inflammation and causes neurocognitive dysfunction in the perioperative period of aging mice.