目的 为观察晚期日本血吸虫感染（简称晚血）小鼠的行为学特征,探讨晚期血吸虫病与焦虑症程度的关系。 方法 取30只6周龄雄性C57BL/6J小鼠,随机分为2组：感染组小鼠（16只）经腹壁皮肤接触感染雌雄尾蚴20条/鼠,未感染组（14只）用不含尾蚴的去氯水处理,两组小鼠于感染后第8周灌服吡喹酮（300 mg/kg）。另设7只6周龄雄性APP/PS1双转基因小鼠（阿尔兹海默症模型小鼠）为阳性对照（转基因组）,不作任何处理。3组小鼠于相同环境饲养至10月龄,观察各组小鼠在旷场试验（OFT）和高架十字迷宫试验（EPM）中的行为变化,以OFT的总路程、中央区路程、中央路程百分比、活动次数、活动时间、中央时间百分比、平均速度、中央平均速度和EPM中的开臂、闭臂和中央区的运动路程、停留时间和进入次数以及开臂内运动路程、停留时间和进入次数的百分比,评价各组小鼠的焦虑样行为。各组小鼠安乐死后,取肝脏,观察肝脏大体形态;肝组织切片经HE和Masson染色后,镜下观察肝脏病理变化和胶原纤维增生情况;测定肝脏胶原纤维特有的羟脯氨酸含量;应用荧光定量PCR检测肝组织α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）、Ⅰ型胶原（ColⅠ）、ColⅢ mRNA相对转录水平。应用SPSS 21.0软件进行统计学分析。 结果 与未感染组比较,感染组小鼠肝脏颜色发暗,肝组织内有大量虫卵沉积,周围有炎性细胞浸润和胶原纤维增生。感染组小鼠的肝脏羟脯氨酸含量为（0.194 ± 0.040）μg/mg,高于未感染组的（0.122 ± 0.016）μg/mg和转基因组的（0.124 ± 0.004）μg/mg（t = 0.79、0.86,均P < 0.05）。感染组小鼠肝脏ColⅠ、α-SMA、TGF-β1、ColⅢ mRNA相对转录水平分别为3.55 ± 1.76、2.01 ± 0.66、2.21 ± 0.64、4.51 ± 2.32,与未感染组比较差异无统计学意义（t = 0.76、0.59、0.17、0.40,均P > 0.05）。感染组小鼠OFT中的活动时间（346.77 ± 181.03）s和 EPM中的开臂内运动路程（206.31 ± 282.52）mm、开臂内运动路程百分比（7.51 ± 9.90）%,以及开臂、闭臂和中央进入次数（1.32 ± 1.51）次、（3.44 ± 3.10）次、（4.53 ± 4.21）次均高于未感染组（t = 1.61、2.24、1.66、1.83、2.35、2.22,P < 0.05或P < 0.01）,两组小鼠的其他指标比较差异均无统计学意义（P > 0.05）。感染组小鼠OFT中的活动次数为（123.68 ± 50.23）次,少于转基因组的（147.90 ± 41.17）次（t = -1.92,P < 0.05）,其他OFT指标比较差异均无统计学意义（P > 0.05）;感染组小鼠EPM中的闭臂内停留时间为（232.85 ± 88.82）s,短于转基因组的（295.38 ± 9.88）s（t = -2.81,P < 0.01）,其他EPM指标均高于转基因组（P < 0.05或P < 0.01）。 结论 晚血小鼠未表现出比未感染组小鼠更严重的焦虑水平,相反呈现出焦虑程度显著减轻的趋势,提示日本血吸虫感染的病理过程可能与焦虑症发生发展无直接相关。

Objective To observe the behavioral characteristics of mice with late-stage schistosomiasis japonica and explore the relationship between late-stage infection of Schistosoma japonicum and anxiety. Methods Thirty 6-week-old male C57BL/6J mice were randomly divided into the infected group (n = 16) and the uninfected group (n = 14). The infected group was infected via abdominal skin contact with 20 cercariae of both sexes, and the uninfected group was treated with dechlorinated water without cercariae. Mice in both of groups were administered with praziquantel by gavage at 8 weeks post-infection. Additional 7 male APP/PS1 double transgenic mice (Alzheimer’s disease model) at 6 weeks of age were used as positive control (transgenic group) without any treatment. Three groups of mice were reared in the same environment until they were 10 months old, to observe their behavioral changes in an open-field test (OFT) and elevated-plus maze test (EPM). In OFT, the total distance, the travelling distance in the central zone, the percentage of travelling distance in the centrol zone, the number of locomotor activity, the duration of locomotor activity, the time percentage spent in the centrol zone, the mean speed, the mean speed in the centrol zone were measured, and in EPM, the locomotor distance, retention time and the number of entry in the open arms/close arms/central zone, and the percentage of locomotor distance, retention time and number of entry in the open arms were recorded to evaluate the anxiety-like behavior of the three mice groups. The mice of all groups were euthanized, and the livers were collected to observe gross morphology. The liver tissue sections were stained using hematoxylin & eosin (HE) and Masson’s trichrome stain for microscopic observation of pathological changes and collagen fiber hyperplasia. The content of liver hydroxyproline which is the specific amino acid constituent in collagen, was determined. The mRNA relative transcription levels of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen Ⅰ(ColⅠ) and ColⅢ in the liver tissues of each group were detected by fluorescence quantitative PCR. SPSS 21.0 software was used for statistical analysis. Results The appaearance color of the mice livers from the infected group was darker compared to the uninfected group. There was a large number of eggs were deposited in the liver tissue, with surrounded infiltrating inflammatory cells and collagen fibres hyperplasia. The liver hydroxyproline content of the infected group (0.194 ± 0.040) μg/mg was significantly higher than that of the uninfected group (0.122 ± 0.016) μg/mg and transgenic group (0.124 ± 0.004) μg/mg (t = 0.79, 0.86, P < 0.05), with no significant difference between the uninfected and transgenic group. The mRNA expression levels of Col Ⅰ, α-SMA, TGF-β1, Col Ⅲ in the liver of the infected group were 3.55 ± 1.76, 2.01 ± 0.66, 2.21 ± 0.64, 4.51 ± 2.32,which is not significantly higher than those of the uninfected group (t = 0.76, 0.59, 0.17, 0.40,P > 0.05). The infected group’s activity time (346.77 ± 181.03) in OFT, the locomotor distance in the open arms (206.31 ± 282.52) mm, the percentage of locomotor distance in the open arms (7.51 ± 9.90)%, the number of entry in the open arms, closed arms and central zone (1.32 ± 1.51, 3.44 ± 3.10, 4.53 ± 4.21)(P < 0.01) in EPM were significantly increased compared to the uninfected group (t = 1.61, 2.24, 1.66, 1.83, 2.35, 2.22, P < 0.05 or P < 0.01), with no significant differences between the two groups for the other indexes. The infected group’s the number of locomotor activity (123.68 ± 50.23) in OFT was significantly decreased compared to the transgenic group (P < 0.05), but there was no significant difference between the two groups for other indexes of OFT. The infected group showed shorter retention time in the closed arm (232.85 ± 88.82) s than that in the transgenic group (295.38 ± 9.88）s(t = -2.81,P < 0.01), and higher values of the rest of the indexes in EPM than those in the transgenic group (P < 0.05 or P < 0.01). Conclusion Mice with late-stage of S. japonica infection did not show more serious level of anxiety than the uninfected mice, however, the anxiety extent presented a significant reducing-tendency, suggesting that the pathological process of S. japonica infection may not be directly correlated to the occurrence and development of anxiety.