Effects of Chuanzhi Tongluo capsules on cognitive function in mice with chronic cerebral hypoperfusion

doi:10.3877/cma.j.issn.1673-9248.2025.05.011

Abstract

Abstract:

Objective

To investigate the effect of Chuanzhi Tongluo caspules on the cognitive function in a mouse model of chronic cerebral hypoperfusion.

Methods

Mice were randomly divided into a sham-operated group (n=15) and an operation group. Chronic cerebral hypoperfusion was induced in the operation group (n=40) via bilateral common carotid artery stenosis (BCAS). The operation group was further randomized into a model group (n=15) and a treatment group (n=15). Starting 2 days after BCAS surgery, the treatment group received 0.2 mL of drug solution daily by gavage for 56 days, while the sham and model groups received equal volumes of 0.9% sodium chloride solution. Cognitive function was assessed using the Morris water maze test, measuring total swimming distance and escape latency on days 1-5, and recording platform crossings on day 6 after platform removal. Cerebral blood flow was measured using laser speckle contrast imaging in 5 randomly selected mice per group at 1, 28, and 56 days post-gavage. Statistical analyses included one-way ANOVA, Welch's ANOVA, or non-parametric tests for between-group comparisons.

Results

Morris water maze results showed that compared with the sham group, mice in the model group swam significantly longer distances on days 3-5 [day 3: (8803.63±1742.95) mm vs (6398.75±2305.12) mm, t=3.071, P=0.004; day 4: (8564.95±1995.25) mm vs (5507.28±3222.72) mm, t=3.067, P=0.004; day 5: 9409.64 (8294.94, 9856.15) mm vs 5010.19(4265.66, 6574.47) mm, H=4.226, P<0.001], had significantly longer escape latencies on days 1-5 [day 1: 60.00(60.00, 60.00) s vs 49.69(44.4700, 60.00) s, H=3.207, P=0.004; day 2: 60.00(45.82, 60.00) s vs 42.61(27.83, 46.94) s, H=3.532, P=0.001; day 3: 52.78(47.21,60.00) s vs 28.19(24.44,38.18) s, H=4.512, P<0.001; day 4: 54.16(42.63, 60.00) s vs 25.09(17.73, 32.38) s, H=3.894, P<0.001; day 5: (51.54±6.27) s vs (30.18±10.34) s, t=5.825, P<0.001], and crossed platforms significantly fewer times on day 6 [ 0.33(0.33, 0.67) times vs 1.67(1.33, 2.00) times, H=4.758, P<0.001]. Compared with the model group mice, mice in the treatment group had significantly shorter distances on day 2 and day 5 [ Day 2: (8306.97±1453.64) mm vs (9632.02±1269.81) mm, t=2.659, P=0.033; Day 5: 5833.10(3777.55, 7606.50) mm vs 9409.64(8294.94, 9856.15) mm, H=3.447, P=0.002], significantly shorter mean escape latencies on day 5 [(34.73±12.51) s vs (51.54±6.27) s, t=5.128, P<0.001], and higher times of crossing the platform on day 6 [1.33(0.67, 1.33) times vs 0.33(0.33, 0.67) times, H=2.579, P=0.030]. The results of laser speckle contrast imaging showed that compared with the sham group, cerebral blood flow was reduced in the model group of mice on days 1, 28, and 56 of gavage [day 1: (65.07±15.85) PU vs (162.20±15.86) PU, t=8.770, P<0.001; day 28: (106.51±23.35) PU vs (192.89±16.46) PU, t=7.943, P<0.001; day 56: 108.72(90.35, 121.28) PU vs 170.75(141.07, 180.06) PU, H=2.616, P=0.027]. The percentage of cerebral hypoperfused area were all significantly higher [day 1: (59.43±12.82)% vs (23.26±2.08)%, t=2.641, P=0.006; day 28: (44.12±3.38)% vs (17.33±1.65)%, t=17.327, P<0.001; day 56: 35.06%(31.78%, 40.26%) vs 22.54%(19.21%,23.08%), H=3.394, P=0.002]. The percentage of cerebral hypoperfused area in mice in the treatment group was significantly less than that in the model group on day 28 [(33.37±1.95)% vs (44.12±3.38)%, t=6.952, P<0.001].

Conclusion

Chuanzhi Tongluo caspules can ameliorate the chronic cerebral hypoperfusion state and cognitive dysfunction in mice after BCAS.

Key words: Chuanzhi Tongluo caspules, Cerebral small vessel disease, Chronic cerebral hypoperfusion, Cognitive dysfunction

Xinru Li, Wenjuan Guo, Yan Yan, Mingqing Wei, Jingnian Ni, Ziyi Long, Ting Li. Effects of Chuanzhi Tongluo capsules on cognitive function in mice with chronic cerebral hypoperfusion[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(05): 435-440.

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Figures/Tables 3

组别	只数	测试第1天[M（Q₁，Q₃）]	测试第2天（ $x ¯$ ±s）	测试第3天（ $x ¯$ ±s）	测试第4天（ $x ¯$ ±s）	测试第5天[M（Q₁，Q₃）]
假手术组	15	11 130.79（9980.36，13 228.07）	7981.64±2529.10	6398.75±2305.12	5507.28±3222.72	5010.19（4265.66，6574.47）
模型组	15	12 195.93（11 777.97，12 778.41）	9632.02±1269.81	8803.63±1742.95^a	8564.95±1995.25^a	9409.64（8294.94，9856.15）^a
治疗组	15	11 146.06（10 678.73，12 193.46）	8306.97±1453.64^c	7332.86±2332.82	7572.23±2827.56^b	5833.10（3777.55，7606.50）^c
统计值		H=3.576	F=4.609	F=4.795	F=4.896	H=20.233
P值		0.167	0.019	0.013	0.012	<0.001

组别	只数	测试第1天[M（Q₁，Q₃）]	测试第2天（ $x ¯$ ±s）	测试第3天（ $x ¯$ ±s）	测试第4天（ $x ¯$ ±s）	测试第5天[M（Q₁，Q₃）]
假手术组	15	11 130.79（9980.36，13 228.07）	7981.64±2529.10	6398.75±2305.12	5507.28±3222.72	5010.19（4265.66，6574.47）
模型组	15	12 195.93（11 777.97，12 778.41）	9632.02±1269.81	8803.63±1742.95^a	8564.95±1995.25^a	9409.64（8294.94，9856.15）^a
治疗组	15	11 146.06（10 678.73，12 193.46）	8306.97±1453.64^c	7332.86±2332.82	7572.23±2827.56^b	5833.10（3777.55，7606.50）^c
统计值		H=3.576	F=4.609	F=4.795	F=4.896	H=20.233
P值		0.167	0.019	0.013	0.012	<0.001

组别	只数	逃避潜伏期（s）					穿越平台次数[次，M（Q₁，Q₃）]
组别	只数	测试第1天[M（Q₁，Q₃）]	测试第2天[M（Q₁，Q₃）]	测试第3天[M（Q₁，Q₃）]	测试第4天[M（Q₁，Q₃）]	测试第5天（ $x ¯$ ±s）	穿越平台次数[次，M（Q₁，Q₃）]
假手术组	15	49.69（44.47，60.00）	42.61（27.83，46.94）	28.19（24.44，38.18）	25.09（17.73，32.38）	30.18±10.34	1.67（1.33，2.00）
模型组	15	60.00（60.00，60.00）^a	60.00（45.82，60.00）^a	52.78（47.21，60.00）^a	54.16（42.63，60.00）^a	51.54±6.27^a	0.33（0.33，0.67）^a
治疗组	15	60.00（60.00，60.00）	45.87（40.24，58.82）	44.66（31.90，51.82）^b	48.14（26.99，54.19）	34.73±12.51^c	1.33（0.67，1.33）^c
统计值		H=10.367	H=12.502	H=20.444	H=15.191	F=8.824	H=22.689
P值		0.006	0.002	<0.001	0.001	<0.001	<0.001

组别	只数	逃避潜伏期（s）					穿越平台次数[次，M（Q₁，Q₃）]
组别	只数	测试第1天[M（Q₁，Q₃）]	测试第2天[M（Q₁，Q₃）]	测试第3天[M（Q₁，Q₃）]	测试第4天[M（Q₁，Q₃）]	测试第5天（ $x ¯$ ±s）	穿越平台次数[次，M（Q₁，Q₃）]
假手术组	15	49.69（44.47，60.00）	42.61（27.83，46.94）	28.19（24.44，38.18）	25.09（17.73，32.38）	30.18±10.34	1.67（1.33，2.00）
模型组	15	60.00（60.00，60.00）^a	60.00（45.82，60.00）^a	52.78（47.21，60.00）^a	54.16（42.63，60.00）^a	51.54±6.27^a	0.33（0.33，0.67）^a
治疗组	15	60.00（60.00，60.00）	45.87（40.24，58.82）	44.66（31.90，51.82）^b	48.14（26.99，54.19）	34.73±12.51^c	1.33（0.67，1.33）^c
统计值		H=10.367	H=12.502	H=20.444	H=15.191	F=8.824	H=22.689
P值		0.006	0.002	<0.001	0.001	<0.001	<0.001

组别	只数	脑血流量（PU）			低灌注区占比（%）
组别	只数	灌胃第1天（ $x ¯$ ±s）	灌胃第28天（ $x ¯$ ±s）	灌胃第56天[M（Q₁，Q₃）]	灌胃第1天（ $x ¯$ ±s）	灌胃第28天（ $x ¯$ ±s）	灌胃第56天[M（Q₁，Q₃）]
假手术组	5	162.20±15.86	192.89±16.46	170.75（141.07，180.06）	23.26±2.08	17.33±1.65	22.54（19.21，23.08）
模型组	5	65.07±15.85^a	106.51±23.35^a	108.72（90.35，121.28）^a	59.43±12.82^a	44.12±3.38^a	35.06（31.78，40.26）^a
治疗组	5	84.12±20.42^b	110.58±8.41^b	126.94（115.39，128.89）	53.73±16.57^b	33.37±1.95^bc	30.94（29.85，31.47）
统计值		F=43.193	F=40.177	H=6.980	F=24.277	F=152.099	H=11.580
P值		<0.001	<0.001	0.031	0.002	<0.001	0.003

组别	只数	脑血流量（PU）			低灌注区占比（%）
组别	只数	灌胃第1天（ $x ¯$ ±s）	灌胃第28天（ $x ¯$ ±s）	灌胃第56天[M（Q₁，Q₃）]	灌胃第1天（ $x ¯$ ±s）	灌胃第28天（ $x ¯$ ±s）	灌胃第56天[M（Q₁，Q₃）]
假手术组	5	162.20±15.86	192.89±16.46	170.75（141.07，180.06）	23.26±2.08	17.33±1.65	22.54（19.21，23.08）
模型组	5	65.07±15.85^a	106.51±23.35^a	108.72（90.35，121.28）^a	59.43±12.82^a	44.12±3.38^a	35.06（31.78，40.26）^a
治疗组	5	84.12±20.42^b	110.58±8.41^b	126.94（115.39，128.89）	53.73±16.57^b	33.37±1.95^bc	30.94（29.85，31.47）
统计值		F=43.193	F=40.177	H=6.980	F=24.277	F=152.099	H=11.580
P值		<0.001	<0.001	0.031	0.002	<0.001	0.003

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