| Background and Objective:Cognitive dysfunction and postoperative cognitive dysfunction?POCD?resulted from diabetes had been paid much attention.The pathogenesis,etiology and the effect of intraoperative blood glucose levels on the occurrence of POCD are not clear.This experiment was designed to investigate the influence of different intraoperative blood glucose levels on POCD of diabetic rats,and to investigate the role of TNF-?,IL-6 and p-Tau protein in POCD of diabetic rats,then provide experiment evidence to control the intraoperative blood glucose level of diabetes.PET/CT scan was used to observe cerebral metabolism,so as to provide the theoretic evidence for the early diaglosis of POCD.Methods:Eighty male healthy SD rats were randomly divided into 2 groups,the control group?group C,n=20?and diabetes mellitus group?group D,n=60?.The diabetic models were copied with high fat and high glucose diet with intraperitoneal injection of streptozotocin to induce blood glucose more than 16.7mmol/L,which defined the models were successful.Continue feeding for 4 weeks until operation experiment.The control group of 20 rats were randomly divided into two groups,blank control group?group C1,n=10?and operation control group?group C2,n=10?.In the diabetic group,40 rats randomly selected from diabetic rats were randomly divided into 4 groups,10 in each group,they were the hypoglycemia group?group D1?,intraoperative blood glucose were less than 3.9mmol/L,the normal blood glucose group?group D2?,intraoperative blood glucose between 3.9 and 11.1mmol/L,the hyperglycemia in group?group D3?,intraoperative blood glucose between 11.1 and 19.4mmol/L,the exceeding hyperglycemia group?group D4?,intraoperative blood glucose more than 19.4mmol/L.Intraoperative blood glucose levels were maintened with insulin and 10%glucose intravenous infusion.The escape latency period and the average swimming speed of place navigation test were detected and recorded by Morris water maze test from the first day to the fourth day after surgery and recorded as dl,d2,d3 and d4.The spatial probe test including frequency of crossing original platform,average swimming speed and average time to explore the original platform quadrant were detected on the fifth day after operation.PET/CT scanning was used to observe cerebral metabolism in the area referred to the memory.The concentration of serum TNF-? and IL-6 were detected with ELISA.Neurons and expression level of p-Tau?Thr231?in hippocampal CA1 were detected by HE and immunochemistry,respectively.Results:1.The results of Morris wate maze test?1?The escape latency period.With the course of training,the escape latency period decreased graduallyin day1,day2,day3 and day4?P<0.05?.There were significant difference of the escape latency period at all points within group C1,C2,D3,D4?P<0.05?.In group D1 and D2,the escape latency period of day 1 was significantly longer than that of day2,day3,day4?P<0.05?,day2 was significantly longer than that of day3,day4?P<0.05?,there were no significant differences between day3 and day4?P>0.05?.The result of between groups,the day1:the escape latency period of group C1 was significantly less than other 5 groups?P<0.05?,the group C2 was significantly less than that of group D1 and D4?P<0.05?,the group D1 was significantly more than group D2 and D3?P<0.05?,group D2 and D3 was significantly less than group D4?P<0.05?.Day2:group C1 was significantly less than that of group C2,D1,D4?P<0.05?,group C2 was significantly less than that of group D1 and D4?P<0.05?,in group D1 was significantly more than group D2 and D3?P<0.05?,group D2 and D3 were significantly less than group D4?P<0.05?.Day3:group C1 was significantly less than the other 5 groups?P<0.05?,group C2 and D2 were significantly less than group D1 and D4?P<0.05?,group D1 and D4 were significantly more than group D3 and D2?P<0.05?.Day4:group C1 was significantly less than the other 5 groups?P<0.05?,C2 group was significantly less than group D1 and D2 and D4?P<0.05?,group D1 was significantly more than group D2 and D3 and D4?P<0.05?,group D2 significantly more than group D3?P<0.05?,the group D2 was significantly less than group D4?P<0.05?,group D3 was significantly less than group D4?P<0.05?.There were no significant difference between other groups?P>0.05?.There were no difference within and between the six groups of the average swim speed?P>0.05?.?2?Spatial probe test.In the experiment of spatial probe test,group D1 to explore the original platform quadrant time was significantly less than group C1?P<0.05?,group D1 and D4 were significantly less than group C1 of times across the platform?P<0.05?,there was no significant difference in the other groups?P>0.05?.The average speed of swimming rats and in the original platform quadrant explore time with no significant difference?P>0.05?.2 The concentration of TNF-? and IL-6The concentration of TNF-? in group C1 was significantly less than the other 5 groups?P<0.05?,group C2 was significantly less than D1,D2,D3,D4 group?P<0.05?,group D2 and D3 was less than that group D4?P<0.05?,there was no significant difference of TNF-? between the other groups?P>0.05?.The concentration of IL-6 in group C1 was significantly less than the other 5 groups?P<0.05?,group C2 was less than group D1,D3 and D4?P<0.05?,group D1 was significantly more than group D2?P<0.05?,group D2 was significantly less than group D3 and D4,there was no significant difference of IL-6 concentration between the other groups?P>0.05?.3.P-Tau(Thr231)level of CA1 area of hippocampusThe value of IOD of p-Tau?Thr231?protein positive neuron in group C1 was significantly less than the diabetic group?P<0.05?,group C2 was significantly less than group D1 and D4?P<0.05?,group D1was significantly more than that of group D2,D3 and D4?P<0.05?,group D2 and D3 were less than that in D4 group?P<0.05?.There were no significant difference of IOD values between the other groups?P>0.05?.4.The results of PET/CT scanThe levels of glucose metabolism were measured in four brain areas.SUV value in group C1 was significantly more than the other 5 groups?P<0.05?,group C2 was significantly more than that of group D1 and D2 and D3 and D4?P<0.05?,group D1 was significantly less than that of group D2 and D3 and D4?P<0.05?,the group D2 was significantly more than that of group D4?value P<0.05?,group D3 was significantly more than that of group D4?P<0.05?.There were no significant difference of SUV values between the other groups?P>0.05?.Conclusion:1.Intraoperative hypoglycemia?<3.9mmol/L?and exceeding hyperglycemia?>19.4mmol/L?could result POCD in diabetic rats.2.POCD after splenectomy related to increased TNF-a and IL-6.POCD resulting from intraoperative exceeding hyperglycemia levels associated with increased TNF-a in diabetes rats.3.POCD resulted from intraoperative hypoglycemia and exceeding hyperglycemia were associated with the increased expression of p-Tau(Thr231)in hippocampal CA1 area.4.Glucose metabolism were reduced in diabetic rats brain after surgery with PET/CT scan,the glucose metabolism of brain tissue in rats of intraoperative hypoglycemia and exceeding hyperglycemia levels decreased significantly. |
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