姜黄素改善缺氧缺血性脑损伤新生大鼠远期神经行为缺陷的机制OACSTPCD

Objective To investigate the pathogenesis of curcumin in reducing the neuroinflammatory and evalu-ate the effect of curcumin on the long-term neurobehavior in neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods The experiment was conducted in the Central Laboratory of Renmin Hospital of Wuhan University from January to June 2023.A total of 59 seven-day-old Sprague-Dawley(SD)rats were selected and randomly divided into sham surgery group(n=15),hypoxic-ischemic brain damage group(HIBD,n=22),and hypoxic-ischemic brain damage+curcumin group(HIBD+curcumin,n=22)using a random number table method.The Longa score was to assess whether or not the model was successful established.Short-term neurobehavioral tests were assessed by negative geotaxis reflex and righting reflex at 48 h after modeling.The long-term neurobehavior were assessed by the cylinder test,morris water maze,comer turn test,and pole-climbing test at 4 weeks after modeling.The brain tissues were collected to detect the levels of inflammatory fac-tors(TNF-α,IL-1β,and IL-6)were detected by Elisa kit and the protein levels(STAT3 and p-STAT3)were detected by Western blot.Results The Longa scores of 1-3 in neonatal rats in the HIBD group(n=18)and the HIBD+curcumin group(n=15)suggested successful modeling.The short-term neurobehavior tests showed that compared to the HIBD group,the HIBD+curcumin group had a shorter negative geotaxis reflex and righting reflex time(F/P=135.037/＜0.001,86.711/＜0.001).The long-term neurobehavioral tests revealed significant improvements in the HIBD+curcumin group com-pared to the HIBD group.The HIBD+curcumin group exhibited increased utilization of the left forelimb in the cylinder test,shortened latency stage to cross the platform in the water maze test,increased number of crossings in the platform quad-rant,decreased scores in the comer test,and reduced climbing time in the pole test(F/P=55.671/＜0.001,102.160/＜0.001,61.455/＜0.001,28.526/＜0.001,51.643/＜0.001).ELISA detection showed that compared with the HIBD group,the HIBD+curcumin group exhibited a significant decrease in the levels of TNF-α,IL-1β,and IL-6 in the brain(F/P=424.753/＜0.001,637.606/＜0.001,361.432/＜0.001).Protein immunoblotting technology showed that compared with the HIBD group,the HIBD+curcumin group significantly decreased the expression levels of p-STAT3/STAT3 in the brain(F/P=26.473/＜0.001).Con-clusion Curcumin can relieve neuroinflammation and improve the long-term neurobehavioral dysfunction by inhibiting STAT3 phosphorylation in HIBD neonatal rat.