【摘要】 目的 探讨黄腐酚（Xn）对孕期感染子代大鼠精神分裂症样行为及小胶质细胞活化和小胶质细胞M1/M2极化的影响。方法 选择20只受孕成功的孕鼠，在孕9.5 d时随机将其分为对照组和聚肌胞苷酸（Poly I:C）组，每组10只；Poly I:C组孕鼠经尾静脉注射10 mg·kg^-1 Poly I:C,对照组孕鼠经尾静脉注射等体积的无菌生理盐水。应用酶联免疫吸附试验（ELISA）法检测2组孕鼠血浆中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。2组孕鼠的子代大鼠于出生21 d时进行离乳，随机取对照组每只孕鼠的子代大鼠2只，共20只，并随机将其分为生理盐水组（n=10）和Xn生理盐水组（n=10）;随机取Poly I:C组每只孕鼠的子代大鼠2只，共20只，并随机将其分为模型组（n=10）和Xn模型组（n=10）。于出生后56～65 d,每天分别从不同组笼中选取1只子代大鼠进行行为学检测，Xn模型组和Xn生理盐水组子代大鼠均于行为学检测开始前1.5 h腹腔注射10 mg·kg^-1 Xn,模型组和生理盐水组子代大鼠于行为学检测开始前1.5 h腹腔注射等体积的无菌生理盐水。采用前脉冲抑制实验（PPI）检测4组子代大鼠的惊吓反应抑制能力，旷场实验检测4组子代大鼠自发活动和焦虑样情绪，高架十字迷宫实验检测4组子代大鼠的焦虑样行为，Y迷宫实验检测4组子代大鼠的记忆功能，被动规避实验检测4组子代大鼠的抑制性回避反应能力；应用蛋白质免疫印迹法检测4组子代大鼠海马组织中分化群（CD）206、几丁质酶3样蛋白3（YM）、环氧化酶-2（COX-2）蛋白相对表达量，ELISA法检测4组子代大鼠TNF-α水平。结果 Poly I:C组孕鼠血浆TNF-α、IL-6水平显著高于对照组（P<0.05）。70、80、85 dB时，模型组子代大鼠PPI抑制率显著低于生理盐水组，Xn生理盐水组及Xn模型组子代大鼠PPI抑制率显著高于模型组（P<0.05）;生理盐水组、Xn生理盐水组及Xn模型组子代大鼠PPI抑制率比较差异无统计学意义（P>0.05）。Xn生理盐水组和Xn模型组子代大鼠旷场的运动总距离显著大于生理盐水组及模型组，Xn模型组子代大鼠旷场的运动总距离显著小于Xn生理盐水组（P<0.05）;生理盐水组与模型组子代大鼠旷场的运动总距离比较差异无统计学意义（P>0.05）。Xn生理盐水组和Xn模型组子代大鼠旷场中心区域运动距离显著大于生理盐水组及模型组，Xn模型组子代大鼠旷场中心区域运动距离显著小于Xn生理盐水组（P<0.05）;生理盐水组与模型组子代大鼠旷场中心区域运动距离比较差异无统计学意义（P>0.05）。4组子代大鼠中心区域运动距离/运动总距离比较差异无统计学意义（P>0.05）。4组子代大鼠进入新异臂次数、T₁及T₂-T₁比较差异无统计学意义（P>0.05）。模型组和Xn模型组子代大鼠海马区CD206蛋白相对表达量显著低于生理盐水组和Xn生理盐水组（P<0.05）;模型组与Xn模型组子代大鼠海马区CD206蛋白相对表达量比较差异无统计学意义（P>0.05）;生理盐水组与Xn生理盐水组子代大鼠海马区CD206蛋白相对表达量比较差异无统计学意义（P>0.05）。4组子代大鼠海马区YM蛋白相对表达量比较差异无统计学意义（P>0.05）。Xn生理盐水组和模型组子代大鼠海马区COX-2蛋白相对表达量显著高于生理盐水组和模型组（P<0.05）;Xn生理盐水组与模型组子代大鼠海马区COX-2蛋白相对表达量比较差异无统计学意义（P>0.05）;生理盐水组和模型组子代大鼠海马区COX-2蛋白相对表达量比较差异无统计学意义（P>0.05）。模型组和Xn模型组子代大鼠小胶质细胞中TNF-α水平显著高于生理盐水组和Xn生理盐水组，Xn模型组子代大鼠小胶质细胞中TNF-α水平显著低于模型组（P<0.05）;生理盐水组与Xn生理盐水组子代大鼠小胶质细胞中TNF-α水平比较差异无统计学意义（P>0.05）。结论 Xn治疗可改善孕期感染子代大鼠的精神分裂症样行为，但对小胶质细胞极化的调节作用不明显，可能通过其他机制发挥治疗作用。更多还原

【Abstract】 Objective To explore the effects of xanthohumol（Xn） on schizophrenia-like behaviors, microglial activation, and microglial M1/M2 polarization in the offspring of pregnant rats infected during pregnancy.Methods A total of 20 successfully conceived mice were selected and then randomly divided into a control group and a polyinosinic-polycytidylic acid（Poly I:C） group at 9.5 days of gestation, with 10 mice in each group.The pregnant mice in the Poly I:C group were injected 10 mg · kg^-1 Poly I:C through the tail vein, while those in the control group were injected an equal volume of sterile saline through the tail vein.The levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in the plasma of pregnant mice in the two groups were detected by enzyme linked immunosorbent assay（ELISA）.Offspring rats of the two groups were weaned on the 21st after birth.Two random offspring rats were selected from each pregnant rat of the control group, totaling 20 offspring rats, which were then randomly divided into a saline group（n=10） and a Xn saline group（n=10）.Similarly, 20 offspring rats were randomly selected from pregnant rats of the Poly I:C group, with 2 offspring rats taken from each pregnant rat.They were then randomly divided into a model group（n=10） and a Xn model group（n=10）.From the 56th to 65th day after birth, one offspring rat of different groups was taken for behavioral testing every day.Offspring rats in both Xn model and Xn saline groups were intraperitoneally injected 10 mg · kg^-1 Xn, while those in both the model and saline groups were intraperitoneally injected an equal volume of sterile physiological saline at 1.5 hours before behavioral testing.The prepulse inhibition experiment（PPI） test was used to assess the inhibitory ability of the four groups of offspring rats to startle reaction.The open field experiment was used to evaluate the spontaneous activity and anxiety-like emotions of offspring rats respectively.The elevated plus maze, Y-maze, and passive avoidance tests were used to detect the anxiety-like behaviors, memory function, and inhibitory avoidance memory ability of offspring rats respectively.The relative expression levels of cluster of differentiation（CD） 206,chitinase-like protein 3（YM）,and cyclooxygenase-2（COX2） proteins in the hippocampal tissue of offspring rats were detected by Western blotting.The levels of TNF-α in offspring rats were measured by ELISA.Results The levels of TNF-α and IL-6 in the plasma of pregnant mice in the Poly I:C group were significantly higher than those in the control group（P<0.05）.At 70,80,and 85 dB,the PPI inhibition rate of offspring rats in the model group was significantly lower than that in the saline group, while the PPI inhibition rates of offspring rats in Xn saline and Xn model groups were significantly higher than those in the model group（P<0.05）.There was no statistically significant difference in PPI inhibition rate among saline, Xn saline, and Xn model groups（P>0.05）.Both the total distance of exercise and the movement distance in the central area in Xn saline and Xn model groups were significantly greater than those in saline and model groups in the open field test（P<0.05）.Both the total distance of exercise and the movement distance in the central area in the Xn model group were significantly shorter than those in the Xn saline group（P<0.05）.There was no statistically significant difference in the total distance of exercise and the movement distance in the central area between saline and model groups（P>0.05）.There was no statistically significant difference in the ratio of the movement distance in the central area to the total distance of exercise among the four groups of offspring rats（P>0.05）.No statistically significant difference was detected in the number of entries to the new arm, T₁,and T₂-T₁ among the four groups of offspring rats（P>0.05）.The relative expression levels of COX2 proteins in the hippocampus tissues of offspring rats in model and Xn model groups were significantly lower than those in saline and Xn saline groups（P<0.05）.There was no statistically significant difference in the relative expression levels of COX2 proteins in the hippocampus tissues of offspring rats between model and Xn model groups, and between saline and Xn saline groups（P>0.05）.No statistically significant difference was observed in the relative expression levels of YM proteins in the hippocampus tissue of offspring rats among the four groups（P>0.05）.The relative expression levels of COX2 protein in Xn saline and Xn model groups were significantly higher than those in saline and model groups（P<0.05）.No statistically significant difference was found in the relative expression levels of COX2 protein between Xn saline and Xn model groups, and between saline and model groups（P>0.05）.The TNF-α levels in microglia of offspring rats in model and Xn model groups were significantly higher than those in saline and Xn saline groups（P<0.05）.The TNF-α levels in microglia of offspring rats in the Xn model group was significantly lower than those in the model group（P<0.05）.There was no statistically significant difference in TNF-α levels in microglia of offspring rats between saline and Xn saline groups（P>0.05）.Conclusion Xn treatment can improve schizophrenia-like behaviors in the offspring of infected pregnant rice, but it is not effective in regulating microglial polarization.Xn may exert therapeutic effects through other mechanisms.更多还原