目的：探讨健脾补肾方对肌萎缩侧索硬化（amyotrophic lateral sclerosis，ALS）AR2小鼠运动和平衡能力的治疗作用及其机制。

方法 ：建立条件性ADAR2（adenosine deaminase acting on RNA 2）基因敲除AR2小鼠模型，选择保留部分运动神经元功能的AR2小鼠48只，随机分为对照组以及健脾补肾方低剂量、中剂量和高剂量组，每组各12只。对照组小鼠除正常饮食外，不给予其他干预。补肾健脾方低、中、高剂量组小鼠分别接受补肾健脾方15mg/kg、30mg/kg、45mg/kg 灌胃，1次/d，连续干预9个月。每个月观察小鼠的体质量、姿势、活动度和生存情况。每3个月检测小鼠的血常规和肝肾功能。分别于干预前以及干预1、3和6个月后对各组小鼠进行疲劳转棒实验、爬杆实验、平衡木实验和跑步机实验。检测不同鼠龄时的ADAR2免疫反应性以及缺失免疫反应性脊髓前角神经元的数量。在干预1和3个月后，检测补肾健脾方各剂量组小鼠的脊髓前角细胞数量。

结果：4组小鼠从干预第3个月起，均出现不同程度的运动能力减退。随着干预的进行，补肾健脾方各剂量组小鼠的运动和平衡能力均较对照组小鼠有所改善。干预3个月后，补肾健脾方中剂量组的疲劳转棒实验、平衡木实验和跑步机实验均显著优于对照组（P＜ 0.05）。干预3个月后，小鼠的ADAR2免疫反应性以及缺失免疫反应性脊髓前角神经元的数量开始减少，与ALS的病程进展一致。干预1个月和3个月后，健脾补肾方中剂量组和高剂量组小鼠的脊髓前角神经元数量均多于对照组。干预期间，小鼠的肝肾功能未见异常。

结论：健脾补肾方（尤其是中剂量）能够改善ALS小鼠的运动和平衡能力，可能与延缓脊髓前角神经元的丢失和变性以及降低AR2小鼠模型的ADAR2免疫反应性有关，且安全性较高。

Objective: To investigate the therapeutic effect of Jian-Pi-Bu-Shen decoction on motor and balance ability in AR2 mice with amyotrophic lateral sclerosis (ALS) and its mechanism.

Methods: The conditional ADAR2 (adenosine deaminase acting on RNA 2) gene knockout AR2 mouse model was established. Forty-eight AR2 mice with partial motor neuron function were selected and randomly divided into control group and Jian-Pi-Bu-Shen decoction groups (low, medium and high dose, respectively), with 12 mice in each group. The mice in the control group were not given interventions except normal diet. The mice in the low-, medium- and high-dose Jian-Pi-Bu-Shen decoction groups received 15 mg/kg, 30 mg/kg and 45 mg/kg of Jian-Pi-Bu-Shen decoction, respectively once a day for 9 months. The body weight, posture, activity and the survival of mice were observed every month. The blood routine and liver and kidney function of mice were measured every 3 months. Before the intervention and 1, 3 and 6 months after the intervention, the mice were tested by rotating fatigue test, climbing rod test, beam balance test and treadmill test. The number of neurons in the anterior horn of spinal cord with immunoreactivity and lack of immunoreactivity of ADAR2 were examined at different ages. After 1 and 3 months of intervention, the number of neurons in the anterior horn of spinal cord was detected.

Results: From the third month of intervention, the motor ability of mice in the four groups decreased in varying degrees. With the intervention, the motor and balance abilities of mice in each dose group of Jian-Pi-Bu-Shen decoction were improved compared with those in the control group. After 3 months of intervention, the results of rotating fatigue test, beam balance test and treadmill test in the medium-dose Jian-Pi-Bu-Shen decoction group were significantly better than those in the control group (P < 0.05). After 3 months of intervention, the number of neurons in the anterior horn of spinal cord with immunoreactivity and lack of immunoreactivity of ADAR2 began to decrease, which was consistent with the progression of ALS. After 1 month and 3 months of intervention, the number of neurons in the anterior horn of spinal cord in the medium-dose and high-dose Jian-Pi-Bu-Shen decoction groups was more than that in the control group. During the intervention, the liver and kidney functions of mice were normal.

Conclusion: Jian-Pi-Bu-Shen decoction (especially medium dose) can improve the motor and balance abilities of AR2 mice, which may be related to delaying the loss and degeneration of neurons in the anterior horn of spinal cord and reducing the ADAR2 immune response of AR2 mice.