| BackgroundPostoperative cognitive dysfunction(POCD)refers to patients without mental disorders before surgery.Neurological complications occur after anesthesia,which are manifested as mental confusion,anxiety,and language and memory learning.Although perioperative management has gradually been emphasized and improved,POCD is still a common postoperative complication,especially in elderly patients.The incidence of constipation in elderly inpatients is about 50%.POCD mostly occurs after major surgery,especially heart and large vessel surgery without clean enema before surgery,up to 60%.The gastrointestinal tract and pelvic surgery require clean enema before surgery,and the incidence of POCD is relatively low,about 10%-20%.Therefore,we propose a scientific hypothesis:clean enema not only reduces the incidence of infection in surgical incisions,but also reduces the change in the number and type of intestinal flora after sevoflurane anesthesia,and reduces intestinal-derived inflammatory factors and pro-inflammatory factors such as Endotoxins enter the brain,thereby reducing the occurrence of POCD and promoting recovery.We used a mouse model of constipation in the elderly to investigate the effects of sevoflurane anesthesia on intestinal permeability,intestinal flora,inflammatory factors and cognitive function.The development of the subject has important clinical significance for the prevention and treatment of POCD,and it points out a new research direction for the research of cognitive impairment related diseases such as Alzheimer's disease.MethodWe selected 140 old(16 month old)male C57 mice,randomly divided into four groups:control group(CTRL),control+evoflurane group(CTRL+S2H),constipation group(LOPER)and constipation+sevoflurane Group(LOPER+S2H).A model of chronic constipation was established by intragastric administration of loperamiade(3 mg/kg)and anesthetized with 2.0%sevoflurane for 2 h.FITC-dextran gavage was used to test the intestinal permeability of each group,bio-plex kit was used to detect changes in inflammatory factors in peripheral blood and brain,and water maze test was used to detect changes in mouse cognitive function.In addition,we performed RNA sequencing on the intestinal flora of each group of mice to observe changes in the number and type of flora.ResultAfter intragastric administration with fluorescein-labeled dextran(FITC-dextran),the content of FITC in the serum of the mice in each group was measured.The results showed that:compared with the control group,the intestinal passage Permeability increased significantly(P<0.05).Inflammatory factor test results showed that:compared with CTRL group,interleukin-1(IL-1)and tumor necrosis factor(TNF)in peripheral blood of mice in CTRL+S2H and LOPER+S2H groups The differences of various inflammatory factors were statistically significant(P<0.05).Immunohistochemical results:Compared with the CTRL group,the number of microglia activated in the PFC region in the brain of LOPER+S2H group was significantly increased(P<0.05).Western blot results showed that compared with the CTRL group,the expressions of nuclear factor kappa-B(NF-?B)and Toll-like receptor 4(TLR4)in the LOPER+S2H group were significantly up-regulated(P<0.01).The water maze experiment showed that the mice in the LOPER+S2H group passed the hidden platform in the navigation test of the water maze significantly less than the control mice(p<0.05).Finally,by sequencing the feces of mice in each group,we found that compared with other groups,the intestinal flora of mice in the LOPER+S2H group changed significantly.ConclusionCompared with normal elderly mice,constipated mice are more likely to cause learning and memory damage after sevoflurane anesthesia.This change may be related to changes in intestinal permeability after sevoflurane anesthesia in mice,changes in peripheral and central inflammatory factors,and changes in intestinal flora. |
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