Impact of salvianolic acid B on cognitive function and GSK-3β/β-Catenin signaling pathway in rats with post-traumatic stress disorder

doi:10.11958/20230179

Abstract

Abstract:

Objective To investigate whether salvianolic acid B (Sal B) can improve the cognitive function in rats with post-traumatic stress disorder (PTSD) by regulating GSK-3β/β-Catenin signal pathway. Methods Sixty rats were randomly grouped into the normal group, the PTSD group, the Sal B low-dose group (10 mg/kg), the Sal B high-dose group (20 mg/kg) and the GSK-3β inhibitor group (30 mg/kg CHIR-99021), with 12 rats in each group. In addition to the normal group, rats in other groups were constructed PTSD rat models by using single prolonged stress (SPS) method. Open field test and Morris water maze test were applied to evaluate the cognitive function of rats. Nissl staining was applied to observe the pathological changes of hippocampal neurons. TUNEL staining was applied to detect the apoptosis of hippocampal neurons. Western blot assay was applied to detect the expression of cleared caspase-3, B-cell lymphoma gene-2-associated X protein (Bax), proto-oncogene (c-Myc), Cyclin D1, total GSK-3β (t-GSK-3β), phosphorylated GSK-3β (p-GSK-3β), total β-Catenin (t-β-Catenin) and phosphorylated β-catenin (p-β-Catenin) proteins in hippocampus. Results Compared with the PTSD group, the number of crawling spaces, standing times, total movement distance and times of crossing the original platform of rats were higher in the Sal B low-dose group, the Sal B high-dose group and the GSK-3β inhibitor group. The escape latency and the time to cross the original platform for the first time were shorter, the apoptosis rate of hippocampal neurons and the expression levels of Bax, cleaved caspase-3, t-GSK-3β and p-β-Catenin proteins in hippocampus were lower, and the expression levels of Cyclin D1, c-Myc, p-GSK-3β, t-β-Catenin proteins were higher (P<0.05). Conclusion Sal B can reduce the apoptosis and damage of hippocampal neurons in rats with PTSD and improve cognitive dysfunction in rats, and inhibit the GSK-3β/β-Catenin signal pathway.

Key words: stress disorders, post-traumatic, Danshensuan B, cognitive dysfunction, glycogen synthase kinase 3, beta Catenin, neurons, apoptosis

CLC Number:

R285.5

Figures/Tables 12

References 29

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组别	爬行格数/个	站立次数/次	运动总距离/cm
正常组	76.33±4.68	14.25±1.46	2 436.18±90.29
PTSD组	48.21±3.95^a	5.17±0.85^a	1 059.67±52.43^a
Sal B低剂量组	61.83±4.40^b	9.08±1.02^b	1 836.29±71.85^b
Sal B高剂量组	72.50±4.06^bc	12.47±1.25^bc	2 345.35±83.86^bc
GSK-3β抑制剂组	69.58±4.12^bc	11.67±1.18^bc	2 308.42±89.27^bc
F	82.233^＊＊	108.915^＊＊	635.255^＊＊

组别	爬行格数/个	站立次数/次	运动总距离/cm
正常组	76.33±4.68	14.25±1.46	2 436.18±90.29
PTSD组	48.21±3.95^a	5.17±0.85^a	1 059.67±52.43^a
Sal B低剂量组	61.83±4.40^b	9.08±1.02^b	1 836.29±71.85^b
Sal B高剂量组	72.50±4.06^bc	12.47±1.25^bc	2 345.35±83.86^bc
GSK-3β抑制剂组	69.58±4.12^bc	11.67±1.18^bc	2 308.42±89.27^bc
F	82.233^＊＊	108.915^＊＊	635.255^＊＊

组别	1 d	2 d
正常组	31.59±4.42	23.47±4.03
PTSD组	75.64±6.83^a	70.95±6.92^a
Sal B低剂量组	56.78±5.97^b	49.26±5.84^b
Sal B高剂量组	43.15±5.62^bc	35.24±5.16^bc
GSK-3β抑制剂组	46.06±4.98^bc	37.58±5.34^bc
F	104.545^＊＊	126.256^＊＊
组别	3 d	4 d
正常组	15.26±3.15	8.95±2.64
PTSD组	67.08±6.54^a	61.24±6.71^a
Sal B低剂量组	41.65±5.23^b	33.17±4.38^b
Sal B高剂量组	30.57±4.31^bc	24.97±3.97^bc
GSK-3β抑制剂组	33.19±4.58^bc	27.12±3.65^bc
F	182.284^＊＊	217.942^＊＊

组别	1 d	2 d
正常组	31.59±4.42	23.47±4.03
PTSD组	75.64±6.83^a	70.95±6.92^a
Sal B低剂量组	56.78±5.97^b	49.26±5.84^b
Sal B高剂量组	43.15±5.62^bc	35.24±5.16^bc
GSK-3β抑制剂组	46.06±4.98^bc	37.58±5.34^bc
F	104.545^＊＊	126.256^＊＊
组别	3 d	4 d
正常组	15.26±3.15	8.95±2.64
PTSD组	67.08±6.54^a	61.24±6.71^a
Sal B低剂量组	41.65±5.23^b	33.17±4.38^b
Sal B高剂量组	30.57±4.31^bc	24.97±3.97^bc
GSK-3β抑制剂组	33.19±4.58^bc	27.12±3.65^bc
F	182.284^＊＊	217.942^＊＊

组别	跨越原平台次数/次	首次跨越原平台时间/s
正常组	9.25±1.38	10.68±1.29
PTSD组	3.42±0.85^a	39.45±3.18^a
Sal B低剂量组	4.83±0.96^b	27.84±2.86^b
Sal B高剂量组	7.67±1.25^bc	19.07±1.95^bc
GSK-3β抑制剂组	7.00±1.04^bc	21.31±2.42^bc
F	51.921^＊＊	233.936^＊＊