Icariin Improves Postoperative Cognitive Dysfunction By Inhibiting Neuroinflammation In Rats

Objective:The purpose of this study was to investigate the effect of Icariin on postoperative cognitive dysfunction and its effect on TLR4/NF-κB signalling pathway.Methods:Thirty-six aged SD rats(20-month-old,600-650 g)were randomly divided into three groups:Control group,Surgery group,Surgery+ICA group.Control group:rats did not undergo surgery;Surgery group:rats received intramedullary fixation of tibial fracture;Surgery+ICA group:rats were given Icariin(60 mg/kg)by gavage after undergoing intramedullary fixation of tibial fracture for 7 consecutive days.Before the surgery,rats in each groups were trained to navigate in the water maze for 7 consecutive days;On the 7th day after the surgery,the water maze space exploration experiment was carried out.The number of platform crossed times,the escape latency and the cumulative residence time in the target quadrant were detected,so as to evaluate the spatial memory ability of the rats.Then the rats were anesthetized to obtain peripheral blood and hippocampal tissue.The morphology and number of neurons in the hippocampus were observed by HE staining and Nissl staining;Inflammatory factor TNF-α,IL-1β,IL-6 level in peripheral blood and hippocampus were detected by ELISA;The activation of microglia in the hippocampus was observed by immunohistochemistry;The expression of TLR4,NF-κB p65,p-NF-κB p65 were detected by Western blot.Results:1.Water maze space exploration experiment results:Compared with the control group,rats in the surgery group decreased the number of platform crossed times,increased the escape latency prolonged,and decreased the cumulative residence time of the target quadrant;Compared with the surgery group,rats the surgery+ICA group increased the number of crossing the platform,decreased the escape latency,and increased the cumulative residence time of the target quadrant.2.HE staining and Nissl staining results:Compared with the control group,the neurons in the CA1,CA3 and DG areas of the hippocampus in the surgery group were more damaged and the number of neurons was decreased;Compared with the surgery group,the neurons in the CA1,CA3 and DG areas of the hippocampus of the surgery+ICA group were slightly injured and the number of neurons increased.3.ELISA results:Peripheral inflammation:Compared with the control group,the peripheral inflammatory factor TNF-α rise in the surgery group,IL-1β and IL-6 level were no significant difference(P>0.05);Compared with surgery group,the peripheral inflammatory factor TNF-α,IL-1β,IL-6 in the surgery group were no significant difference(P>0.05).Hippocampal neuroinflammation:Compared with the control group,the inflammatory factor TNF-α,IL-1β,IL-6 level increased in the hippocampus of the surgery group rats;Compared with surgery group,the inflammatory factor TNF-α,IL-1β,IL-6 level decreased in hippocampus of surgery+ICA group rats.4.Immunohistochemical results:Compared with the control group,the number of activated microglia in the hippocampus of the surgery group increased,and microglia were activated;Compared with the surgery group,the number of activated microglia in the hippocampus of Surgery+ICA group decreased,and the activation of microglia was inhibited.5.Western blot results:Compared with control group,the expression of TLR4 and p-NF-κB p65 protein in hippocampus of surgery group rats increased;Compared with surgery group,the expression of TLR4 and p-NF-κB p65 in hippocampus of surgery+ICA group rats decreased.Conclusion:Icariin can improve the spatial memory ability of rats after surgery,reduce the damage of neurons in the hippocampus induced by surgery,reduce the level of neuroinflammation in the hippocampus,and inhibit the activation of microglia in the hippocampus.These effects of Icariin may be related to the inhibition of TLR4/NF-κB signal path.