RESUMEN
OBJECTIVE@#To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND).@*METHODS@#Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test.@*RESULTS@#In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05).@*CONCLUSION@#In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.
Asunto(s)
Masculino , Animales , Ratas , Ratas Sprague-Dawley , Puente Cardiopulmonar , Microbioma Gastrointestinal , Interleucina-6 , Factor de Necrosis Tumoral alfa , Trastornos NeurocognitivosRESUMEN
Objective:To evaluate the mechanism of α7 nicotinic acetylcholine receptor (α7nAChR) agonist-induced protection of the intestine in rats undergoing cardiopulmonary bypass (CPB) and the relationship with the activity of enteric glial cells (EGCs).Methods:Seventy-two clean-grade adult male Sprague-Dawley rats, aged 400-500 g, were divided into 3 groups ( n=24 each) using a random number table method: sham operation group (group S), CPB group (group C) and α7nAChR agonist PHA568487 plus CPB group (group P). In group P, PHA568487 0.8 mg/kg was intraperitoneally injected, and 30 min later CPB model was established.At the beginning of CPB (T 0), at 1 h of CPB (T 1), and at 2 and 6 h after termination of CPB (T 2, 3), the rats were sacrificed, and intestinal tissues were obtained for examination of the pathological changes and for determination of the expression of ZO-1, occludin, glial fibrillary acidic protein (GFAP), and calcium-binding protein (S-100β protein) by Western blot.The immunohistochemical method was used to observe the positive expression of GFAP at T 2. Results:Compared with group S, the expression of GFAP and S-100β protein was significantly up-regulated, and the expression of ZO-1 and occludin was down-regulated at T 1-3( P<0.05), the positive expression of GFAP was increased, and the intestinal tissue injury was accentuated in C and P groups.Compared with group C, the expression of GFAP, ZO-1 and occludin was significantly up-regulated, and the expression of S-100β protein was down-regulated at T 1-3( P<0.05), the positive expression of GFAP was increased, and the intestinal tissue injury was reduced in group P. Conclusion:The mechanism by which α7nAChR agonist attenuates intestinal injury may be related to activating EGCs and improving intestinal barrier function in rats undergoing CPB.