| Objective:To investigate whether paricalcitol supplementation can improve cognitive dysfunction associated with chronic pain and its possible mechanism.Methods: forty nine-week-old SD rats were randomly divided into Sham operation group(Sham group,n=10),thoracotomy operation group(Surgery group,n=10),paricalcitol only group(Sham+Pari group,n=10)and paricalcitol combined thoracotomy and Surgery+Pari group(Surgery+Pari group,n=10).The Surgery+Pari group and Sham+Pari group were respectively given intraperitoneal injection of paricalcitol0.5μg/kg/ time,once a day,for 5 consecutive days before Surgery,and paricalcitol was supplemented once a day after Surgery,0.5μg/kg/ time,until 28 days after Surgery.Sham group and Surgery group were given equal doses of normal saline.Thoracotomy was performed in Surgery group and Surgery+Pari group.Sham operation was performed in Sham group and Sham+Pari group.Mechanical pain threshold tests were performed at 3,7,14,21 and 28 days postoperatively.The cognitive and behavioral changes of rats were detected by open field test,new object test and Barnes maze test on 28 days after operation.The rats in each group were sacrificed 35 days after the operation and the samples were taken.MRNA expression levels of N-methyl-D-aspartate receptor subunits(NR1,NR2 A,NR2B),α-amino-3-hydroxy-5-methyl-4-isooxazolpropionic acid receptor subunits(Glu A1,Glu A2),TNF-α and IL-1β in hippocampal region of rats were detected by RT-PCR.Meanwhile,the activation of microglia in hippocampus was detected by immunofluorescence.Cecal stool samples were collected from each group on day 35 to analyze the difference of intestinal flora.Results: 1.Compared with the Sham group,the mechanical pain threshold in the Surgery group was significantly reduced on the 3rd,7th,14 th,21st and 28 th day after Surgery.2.Open field test showed that there was no significant difference in exercise ability among all groups.The new object experiment showed that the rats in the Surgery group had a lower preference for new objects than the Sham group,while the preference index in the Surgery+Pari group was higher than that in the Surgery group,and there was no difference between the Sham+Pari group and the Sham group.Barnes Maze showed that the incubation period and the number of errors in the Sham+Pari group showed no significant difference compared with the Sham group at28 days after Surgery,while the incubation period and the number of errors in the Surgery group significantly increased.Compared with the Surgery group,latency and error times of the Surgery+Pari group were significantly reduced,while there was no difference between the Sham+Pari group and the Sham group.3.Rt-pcr showed that compared with Sham group,the expression of NR2 B in the hippocampus of Surgery group was down-regulated;Compared with the Surgery group,the expression of NR2 B in the hippocampus of the Surgery+Pari group was up-regulated,and there was no difference between the Sham+Pari group and the Sham group.Compared with Sham,il-1 β and TNF-α expressions were up-regulated in Surgery group.Compared with the Surgery group,the expressions of IL-1β and TNF-α in Surgery+Pari group were down-regulated,and there was no difference between Sham+Pari group and Sham group.Immunofluorescence showed that compared with Sham,microglia in the hippocampal area of Surgery group were significantly activated.Compared with the Surgery group,the activation of microglia in the hippocampus of the Surgery+Pari group was not significant,and there was no difference between the Sham+Pari group and the Sham group.4.Compared with the Sham group,intestinal flora in the Surgery group changed significantly,and this change was partially reversed in the Surgery+Pari group.Conclusions: Parietal supplementation improves the cognitive dysfunction associated with chronic pain after thoracotomy in rats,and the mechanism may be related to the reduction of neuroinflammation by changing intestinal flora There are 15 figures,0 tables and 63 references... |
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