Objectives: To investigate the effects of α1-antitrypsin (AAT) on motor function in adult mice with immature brain white matter injury.
Methods: Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group (n=27), hypoxia-ischemia (HI) + saline group (n=27), and HI+AAT group (n=27). The HI white matter injury mouse model was established using HI methods. The HI+AAT group received intraperitoneal injections of AAT (50 mg/kg) 24 hours before HI, immediately after HI, and 72 hours after HI; the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points. Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling. At 2 months of age, adult mice were evaluated for static, dynamic, and coordination parameters using the Catwalk gait analysis system.
Results: Compared to the sham surgery group, mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling, indicating significant white matter injury. The white matter injury persisted at 55 days after modeling. In comparison to the sham surgery group, the HI+saline group exhibited decreased paw print area, maximum contact area, average pressure, maximum pressure, paw print width, average velocity, body velocity, stride length, swing speed, percentage of gait pattern AA, and percentage of inter-limb coordination (left hind paw → left front paw) (P<0.05). The HI+saline group showed increased inter-paw distance, percentage of gait pattern AB, and percentage of phase lag (left front paw → left hind paw) compared to the sham surgery group (P<0.05). In comparison to the HI+saline group, the HI+AAT group showed increased average velocity, body velocity, stride length, and swing speed (right front paw) (P<0.05).
Conclusions: The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood, while the use of AAT can improve some aspects of their motor function.
目的: 探讨α1-抗胰蛋白酶（α1-antitrypsin, AAT）对未成熟脑白质损伤小鼠成年期运动功能的影响。方法: 将5日龄C57BL/6J幼鼠随机分为假手术组（n=27）、缺氧缺血（hypoxia-ischemia, HI）+生理盐水组（n=27）、HI+AAT组（n=27）。通过HI法建立未成熟脑白质损伤小鼠模型。HI+AAT组分别于HI前24 h、HI后立即及HI后72 h腹腔注射AAT（50 mg/kg）；HI+生理盐水组在相同时间腹腔注射相同剂量生理盐水。造模后7 d和55 d进行头颅磁共振T2加权成像扫描。2月龄时利用Catwalk步态分析系统评估成年期小鼠的静态、动态和协调性参数。结果: 与假手术组小鼠相比，HI损伤小鼠造模后7 d头颅磁共振T2加权像呈现高信号，可见脑白质明显损伤；造模后55 d脑白质损伤仍存在。与假手术组小鼠相比，HI+生理盐水组小鼠爪印面积、最大接触面积、平均压强、最大压强、爪印宽度、平均速度、身体速度、步幅长度、摆动速度、步态模式AA占比、爪印耦合（左后爪→左前爪）占比降低（P<0.05）；HI+生理盐水组爪间距离、步态模式AB占比、位相滞后（左前爪→左后爪）占比升高（P<0.05）。与HI+生理盐水组小鼠相比，HI+AAT组小鼠平均速度、身体速度、步幅长度、摆动速度（右前爪）升高（P<0.05）。结论: 未成熟脑白质损伤小鼠在成年期可表现出明显运动功能障碍，而应用AAT可改善其部分运动功能。.
Keywords: Alpha-1 antitrypsin; Catwalk gait analysis; Hypoxia-ischemia; Mouse; White matter injury.