Effect of astaxanthin on postoperative cognitive dysfunction in type 2 diabetes mellitus mice
Objective To investigate the ameliorative effects and possible mechanisms of astaxanthin on postoperative cognitive dysfunction(POCD)in type 2 diabetes mellitus mice.Methods Forty-eight male C57BL/6J mice received high-fat diet and were intraperitoneally injected with nicotinamide and streptozotocin to prepare type 2 diabetes mellitus models.Thirty-six mice models were randomly divided into control,model and astaxanthin groups,with 12 mice in each group.The POCD models were constructed by laparotomy under sevoflurane anesthesia in model and astaxanthin groups,and control group only received normal diet without laparotomy.Astaxanthin group was injected intraperitoneally with 30 mg/(kg·d)of astaxanthin,while control and model groups were injected with an equal volume of normal saline,totally for 3 d.The body mass and plasma glucose before laparotomy,and swimming speed after laparotomy were compared among three groups.After modeling,Morris water maze test was done to assess the cognitive function(escape latency,number of platform crossings,and percentage of time spent in the target quadrant),and immunofluorescence was used to detect the relative fluorescence intensity of ionized calcium-binding adaptor molecule 1(Iba1)and the percentage of A1 astrocytes in the hippocampus,the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1α,and complement 1q(C1q)in the hippocampus were detected by ELISA,and the relative expressions of postsynaptic density protein(PSD)95 and synaptophysin(SYP)protein in the hippocampus were detected by Western blot.Results There were no significant differences in the preoperative body mass,preoperative plasma glucose and postoperative swimming speed among three groups(P＞0.05).The escape latency was longer in model group[(34.58±10.54)s]than that in astaxanthin group[(24.63±7.79)s]and control group[(15.56±5.73)s](P＜0.05),and longer in astaxanthin group than that in control group(P＜0.05).The number of platform crossings and the percentage of time spent in the target quadrant were less in model group[(2.92±1.08)times,(29.04±10.30)％]than those in astaxanthin group[(5.33±1.50)times,(41.04±9.20)％]and control group[(6.25±2.09)times,(54.40±10.16)％](P＜0.05),the percentage of time spent in the target quadrant was less in astaxanthin group than that in control group(P＜0.05),and the number of platform crossings showed no significant difference between astaxanthin and control groups(P＞0.05).The relative fluorescence intensity of Iba1,A1 astrocytes percentage,and levels of TNF-α,IL-1α and C1q were higher in model group[(7 951.09±1 818.78)AU,(50.93±8.84)％,(59.27±21.44)pg/mg prot,(22.94±6.81)pg/mg prot,(9.35±3.62)pg/mg prot]than those in astaxanthin group[(4 345.32 士 989.66)AU,(25.23±7.48)％,(35.17 士12.16)pg/mg prot,(15.36±4.22)pg/mg prot,(5.79±1.61)pg/mg prot]and control group[(3 038.24±301.92)AU,(18.72±3.06)％,(20.26±6.86)pg/mg prot,(7.96±1.71)pg/mg prot,(3.83±1.13)pg/mg prot](P＜0.05),and the relative expressions of PSD95 and SYP proteins were lower in model group(0.42±0.17,0.64±0.18)than those in astaxanthin group(0.80±0.21,0.91±0.15)and control group(1.00±0.22,1.00±0.13)(P＜0.05).The level of IL-1α was higher in astaxanthin group than that in control group(P＜0.05),while the relative fluorescence intensity of Iba1,A1 astrocytes percentage,levels of TNF-α and C1q,and relative expressions of PSD95 and SYP proteins showed no significant differences between astaxanthin group and control group(P＞0.05).Conclusion Astaxanthin can improve POCD in type 2 diabetes mellitus mice,possibly by inhibiting the hippocampal microglia activation and its mediated inflammatory response,reducing the polarization of A1 astrocytes,and thus increasing the number of synapses in the hippocampus.
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