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中华脑血管病杂志(电子版)

中华脑血管病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (04) : 324 -331. doi: 10.3877/cma.j.issn.1673-9248.2025.04.010

基础研究

L-茶氨酸对大鼠脑缺血模型神经功能的影响
闫江婷1, 王静茹2, 杨莹3, 林莉瑶1, 杨叶1, 黄晓松3,†(), 曾贵荣2,†()   
  1. 1　410218　长沙，湖南中医药大学临床医学院
    2　410329　长沙，湖南省药物安全评价研究中心&新药药效与安全性评价湖南省重点实验室
    3　410000　长沙，湖南省第二人民医院　湖南省脑科医院神经内科
  • 收稿日期:2024-11-21 出版日期:2025-08-01
  • 通信作者: 黄晓松, 曾贵荣
  • 基金资助:
    湖南省自然科学基金(2025JJ90021); 湖南中医药大学研究生创新项目(2024CX142); 湖南中医药大学校院联合基金项目(2024XYLH202)

Effect of L-theanine on neural function in rat model of cerebral ischemia

Jiangting Yan1, Jingru Wang2, Ying Yang3, Liyao Lin1, Ye Yang1, Xiaosong Huang3,†(), Guirong Zeng2,†()   

  1. 1 Clinical Medicine School, Hunan University of Traditional Chinese Medicine, Changsha 410218, China
    2 Hunan Key Laboratory of Drug Efficacy and Safety Evaluation & Hunan Drug Safety Evaluation Research Center, Changsha 410329, China
    3 Department of Neurology, the Second People's Hospital of Hunan Province, Hunan Brain Hospital, Changsha 410208, China
  • Received:2024-11-21 Published:2025-08-01
  • Corresponding author: Xiaosong Huang, Guirong Zeng
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引用本文：

闫江婷, 王静茹, 杨莹, 林莉瑶, 杨叶, 黄晓松, 曾贵荣. L-茶氨酸对大鼠脑缺血模型神经功能的影响[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(04): 324-331.

Jiangting Yan, Jingru Wang, Ying Yang, Liyao Lin, Ye Yang, Xiaosong Huang, Guirong Zeng. Effect of L-theanine on neural function in rat model of cerebral ischemia[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(04): 324-331.

目的

探讨L-茶氨酸对局灶性脑缺血模型大鼠神经功能的作用。

方法

将SPF级100只雄性SD大鼠随机分为假手术组、模型组。模型组大鼠采用线栓法建立大鼠局灶性脑缺血性模型，选取存活大鼠根据神经功能评分随机分为模型对照组、依达拉奉注射液组（0.9 mg/kg），L-茶氨酸低、中、高剂量（50、100、200 mg/kg）组，假手术组及模型对照组均给予等体积纯水灌胃，其余各组动物给予相应药物灌胃，每天1次，连续给药14 d，分别于给药后7 d、14 d进行神经功能评分、抓力测试、双足平衡测试，末次给药后进行步态分析、脑血流量检测，取脑组织进行组织病理学检查。上述指标多组间比较采用单因素方差分析，采用LSD-t检验比较模型对照组与假手术组、模型对照组与其他各给药组的差异。

结果

局灶性脑缺血模型大鼠出现运动功能障碍，在给药后7 d、14 d神经功能评分[（3.0±0.0）分、（3.0±0.0）分]均较假手术组[（0.0±0.0）分、（0.0±0.0）分]显著升高（t=0.679、2.208，P均=0.001）。模型对照组大鼠在给药后7 d、14 d左右后肢压力差[（62.0±40.8）g、（80.3±32.2）g]均较假手术组[（3.7±2.7）g、（5.0±2.1）g]显著升高（t=2.707、2.608，P=0.032、0.002），抓力在给药后7 d、14 d[（321.9±28.5）g、（424.1±62.6）g]均较假手术组[（811.6±60.8）g、（988.5±54.9）g]显著降低（t=20.632、19.166，P均=0.001）。给药后14 d大鼠步态指标平均体转角[（119.2±28.8）度]较假手术组[（15.5±9.0）度]显著增加（t=9.127，P=0.005），左侧步基[（3.0±2.3）]、速度[（234.9±62.0）mm/s]、右前摆动时长[（0.04±0.02）s]、右后足压力[（28.6±2.1）g]均较假手术组[（336.0±32.5）、（986.5±292.6）mm/s、（0.13±0.02）s、（51.2±7.5）g]显著降低，差异均有统计学意义（t=9.127、26.580、2.531、6.742、4.031，P=0.005、0.001、0.001、0.001、0.001）。与模型对照组比较，L-茶氨酸低、中、高剂量能显著降低给药7 d、14 d大鼠神经功能评分和给药14 d左右后肢压力差，中、高剂量能显著升高大鼠14 d抓力，低、中、高剂量能显著减少大鼠平均体转角并显著升高左侧步基、速度、右前摆动时长、右后足压力，差异均有统计学意义（P均<0.05）。L-茶氨酸中、高剂量能显著升高脑缺血模型大鼠脑血流量（P均<0.05），且能显著降低脑组织神经纤维轻度肿胀，间质性水肿和炎症细胞浸润。

结论

L-茶氨酸可显著改善脑缺血后运动功能障碍，增加脑血流量，减轻脑组织病理变化，对脑卒中后神经功能损伤具有显著的保护作用。

关键词: L-茶氨酸, 脑缺血, 大鼠, 神经功能
Objective

To investigate the protective effect of L-theanine on nerve function in rats with focal cerebral ischemia.

Methods

One hundred male SPF-grade SD rats were randomly divided into a sham-operated group and a model group. Focal cerebral ischemia was induced in the model group using the thread embolism method. The surviving rats were randomly assigned model control group, Edaravone injection group (0.9 mg/kg), low, medium and high doses of L-theanine (50, 100, 200 mg/kg) according to neural function scores. The sham-operated group and the model control group received an equal volume of pure water via intragastric administration, while the other groups received their respective treatments once a day for 14 consecutive days. Neurological function score, grip strength, and bipedal balance were tested at 7 and 14 days after administration, respectively. Gait analysis and cerebral blood flow measurements were performed after the final administration, followed by histopathological examination of brain tissue. One-way ANOVA was used for comparison between multiple groups, and LSD-t test was used for intergroup comparisons.

Results

In the focal cerebral ischemia rat model, significant motor dysfunction was observed. On days 7 and 14, the model group showed significantly higher neurological function scores (3.0±0.0 vs 0.0±0.0 in sham-operated group; t=0.679, 2.208, all P=0.001), increased hindlimb pressure difference [D7: (62.0±40.8) g; D14: (80.3±32.2) g vs sham-operated group: (3.7±2.7) g and (5.0±2.1) g; t=2.707, 2.608, P=0.032, 0.002], and reduced grip strength [D7: (321.9±28.5) g; D14: (424.1±62.6) g vs sham-operated group: (811.6±60.8) g and (988.5±54.9) g; t=20.632, 19.166, all P=0.001]. After 14 days, the model group also exhibited a greater average body rotation angle [(119.2±28.8)° vs (15.5±9.0)°; t=9.127, P=0.005], and reduced left step width (3.0±2.3 vs 336.0±32.5; t=26.580, P=0.001), speed [(234.9±62.0) mm/s vs (986.5±292.6) mm/s; t=2.531, P=0.001], right forelimb swing duration [(0.04±0.02) s vs (0.13±0.02) s; t=6.742, P=0.001], and right hindfoot pressure [(28.6±2.1) g vs (51.2±7.5) g; t=4.031, P=0.001]. Compared to the model control group, all doses of L-theanine significantly reduced neurological scores and hindlimb pressure differences from day 7 to 14 (all P<0.05). The medium and high doses significantly increased grip strength on D14 (all P<0.05). All L-theanine doses improved gait parameters, including increased left step width, speed, right forelimb swing duration, and right hindfoot pressure (all P<0.05). Medium and high doses of L-theanine also enhanced cerebral blood flow and alleviated pathological changes such as mild neural fiber swelling (all P<0.05), interstitial edema, and cellular infiltration.

Conclusion

L-theanine can significantly improve the motor dysfunction after cerebral ischemia, increases cerebral blood flow, reduces brain tissue pathology, and exerts a notable protective effect on neurological function following cerebral ischemia.

Key words: L-theanine, Cerebral ischemia, Rat, Neurological function
表1 各组大鼠脑缺血模型神经功能评分比较（分，
）
组别 只数 给药前 给药后7 d 给药后14 d
假手术组 10 0.0±0.0 0.0±0.0 0.0±0.0
模型对照组 10 3.1±0.1a 3.0±0.0a 3.0±0.0a
依达拉奉注射液组 10 2.5±0.2a 2.0±0.0b 2.0±0.0b
L-茶氨酸低剂量组 10 3.1±0.3a 2.0±0.0b 2.0±0.0b
L-茶氨酸中剂量组 10 2.9±0.2a 2.3±0.3b 1.6±0.2b
L-茶氨酸高剂量组 10 2.4±0.2a 2.0±0.0b 1.7±0.3b
F值 46.233 44.571 48.852
P值 <0.001 <0.001 <0.001
表2 各组大鼠抓力比较（g，
）
组别 只数 给药后7 d 给药后14 d
假手术组 10 811.6±60.8 988.5±54.9
模型对照组 10 321.9±28.5a 424.1±62.6a
依达拉奉注射液组 10 499.6±137.6b 600.6±43.3b
L-茶氨酸低剂量组 10 371.3±75.3 487.0±86.1
L-茶氨酸中剂量组 10 351.2±94.4 533.9±98.6b
L-茶氨酸高剂量组 10 400.3±104.1 590.5±111.3b
F值 37.056 49.793
P值 <0.001 <0.001
表3 各组大鼠左右后肢压力差（右足－左足）比较（g，
）
组别 只数 给药后7 d 给药后14 d
假手术组 10 3.7±2.7 5.0±2.1
模型对照组 10 62.0±14.7a 80.3±14.2a
依达拉奉注射液组 10 2.8±1.0b 35.1±11.8b
L-茶氨酸低剂量组 10 12.9±6.4 42.4±6.7b
L-茶氨酸中剂量组 10 59.5±27.9 41.0±10.8b
L-茶氨酸高剂量组 10 57.1±21.6 39.0±12.4b
F值 2.593 2.784
P值 0.045 <0.001
表4 各组大鼠步态指标的比较（
）
组别 只数 平均体转角（度） 左侧步基 速度（mm/s） 右前摆动时长（s） 右后足压力（g）
假手术组 10 15.5±9.0 336.0±32.5 986.5±292.6 0.13±0.02 51.20±7.5
模型对照组 10 119.2±28.8a 3.0±2.3a 234.9±62.0a 0.04±0.02a 28.6±2.1a
依达拉奉注射液组 10 4.4±3.4b 63.0±10.3b 717.8±8.2b 0.22±0.08b 93.3±7.2b
L-茶氨酸低剂量组 10 3.7±3.0c 24.5±9.5c 692.6±377.6c 0.07±0.02c 98.0±5.8c
L-茶氨酸中剂量组 10 6.2±1.6d 30.0±9.0d 872.1±30.7d 0.13±0.04d 74.0±5.9d
L-茶氨酸高剂量组 10 1.8±1.1e 102.0±39.6e 1096.4±78.0e 0.06±0.01e 71.3±8.5e
F值 11.951 28.176 23.028 30.006 18.829
P值 <0.001 <0.001 <0.001 <0.001 <0.001
图1 L-茶氨酸对脑缺血大鼠模型体转角的影响。图a~f分别为假手术组、模型对照组、依达拉奉注射液组、L-茶氨酸低剂量组、L-茶氨酸中剂量组、L-茶氨酸高剂量组图像
图2 L-茶氨酸对脑缺血大鼠模型右后足压力的影响。图a~f分别为假手术组、模型对照组、依达拉奉注射液组、L-茶氨酸低剂量组、L-茶氨酸中剂量组、L-茶氨酸高剂量组图像
表5 各组大鼠脑血流量的比较（
）
组别 只数 脑血流量（PU）
假手术组 10 138.3±1.6
模型对照组 10 30.4±14.4a
依达拉奉注射液组 10 74.8±27.4b
L-茶氨酸低剂量组 10 31.8±12.6
L-茶氨酸中剂量组 10 110.4±10.8b
L-茶氨酸高剂量组 10 87.5±16.5b
F值 14.591
P值 <0.001
图3 各组大鼠脑血流量的激光散斑血流成像图。图a~f分别为假手术组、模型对照组、依达拉奉注射液组、L-茶氨酸低剂量组、L-茶氨酸中剂量组、L-茶氨酸高剂量组图像
图4 各组大鼠脑组织病理图（苏木精-伊红染色，×100）。图a~f分别为假手术组、模型对照组、依达拉奉注射液组、L-茶氨酸低剂量组、L-茶氨酸中剂量组、L-茶氨酸高剂量组图像
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