鹿茸多肽对轻度认知功能障碍大鼠学习记忆能力的改善作用及其调节Keap1/Nrf2 /HO-1信号通路的机制

doi:10.13481/j.1671-587X.20210519

Abstract

Abstract: Objective

To observe the effects of velvet antler polypeptide（VAP） on the learning and memory abilities and the expressions of KELCH-like ECH related protein 1（Keap1）， nuclear factor E2 related factor 2（Nrf2） and heme oxygenase-1（HO-1） in hippocampus tissue of the rats with mild cognitive impairment（MCI）， and to explore the mechanisms.

Methods

Fifty clean Wistar rats were randomly divided into normal control group， MCI group， piracetam group， low dose of VAP group and high dose of VAP group （n=10）. Except normal control group，the rats in other groups were intraperitoneally injected scopolamine for 18 d to set up the MCI models.The rats in piracetam group were given piracetam 500 mg·kg^－1， the rats in low dose of VAP group were given VAP 200 mg·kg^－1， and the rats in high dose of VAP group waere given VAP 300 mg·kg^－1. The behavioral changes of rats in various groups were observed by Morris water maze test， the pathomorphology of hippocampus tissue of the rats was observed by HE staining， the activities of superoxide dismutase （SOD） and the levels of malondialdehyde （MDA） in serum of the rats in various groups were detected by ELISA method， and the expression levels of Keap1， Nrf2and HO-1 proteins in hippocampus tissue of the rats in various groups were detected by Western blotting method.

Results

The results of Morris water maze test showed that compared with normal control group， the escape latency and behavior path of the rats in MCI group were significantly increased （P<0.01）， while the times of crossing the platform and the residence time in the effective area were significantly decreased （P<0.01）；compared with MCI group， the escape latencies of piracetam group，low dose of VAP group and high dose of VAP group were decreased significantly （P<0.01），the behavior paths of piracetam group and high dose of VAP group were shortened significantly （P<0.01）， and the times of crossing the platform and the residence time in the effective area of the rats in piracetam group，low dose of VAP group and high dose of VAP group were increased significantly （P<0.05 or P<0.01）.The HE results showed that compared with normal control group， the number of cells in hippocampus tissue of the rats in MCI group was decreased obviously， and the arrangement mode was changed from orderly to relatively disorder； compared with MCI group， the cells in hippocampus tissue of the rats in piracetam group and high dose of VAP group were arranged more orderly and the shape was slightly regular. Compared with normal control group， the activity of serum SOD of the rats in MCI group was decreased significantly （P<0.01） and the level of MDA was increased significantly （P<0.01）；compared with MCI group， the serum SOD activities of the rats in piracetam group and high dose of VAP group were increased significantly （P<0.05 or P<0.01）， while the MDA levels were decreased significantly （P<0.05 or P<0.01）.The results of Western blotting method showed that compared with normal control group， the expression level of Keap1 protein in hippocampus tissue of the rats in MCI group was significantly increased （P<0.01），while the expression levels of Nrf2 and HO-1 proteins were significantly decreased （P<0.05 or P<0.01）；compared with MCI group， the expression levels of Keap1 protein in hippocampus tissue of the rats in piracetam group， low dose of VAP group and high dose of VAP group were decreased significantly （P<0.01）， while the expression levels of Nrf2 and HO-1 proteins were increased significantly （P<0.01）.

Conclusion

VAP can improve the learning and memory abilities of MCI model rats induced by scopolamine， and its mechanism may be related to increasing the expression levels of Keap1，Nrf2 and HO-1 proteins in hippocampus of the rats to play an anti-oxidative stress role.

Key words: velvet antler polypeptide, mild cognitive impairment, scopolamine, KELCH-like ECH-associated protein 1, nuclear factor-E2-related factor 2, heme oxygenase 1

CLC Number:

R285.5

Xiaowei HUANG,Yuexin LIU,Jinji WANG,Jiaming XU,Qiuzhu TANG,He LIN,Jixiang REN,Tianye LAN. Improvement effects of pilose antler polypeptide on learning and memory abilities in rats with mild cognitive impairment and their mechanisms of regulating Keap1/Nrf2 /HO-1 signaling pathway[J].Journal of Jilin University(Medicine Edition), 2021, 47(5): 1215-1220.

Figures/Tables 5

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References 20

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Group	Escape latency(t/s)	Behavior path(l/cm)	Times of crossing platform (n)	Residence time in effective area(t/s)
Normal control	48.70±4.06	467.40±28.10	14.60±1.40	87.33±2.97
MCI	97.36±4.06^*	792.06±20.85^*	5.10±1.10^*	58.41±2.70^*
Piracetam	71.36±4.44^△△	578.63±28.96^△△	12.80±1.30^△△	77.70±2.88^△△
Low dose of VAP	88.12±3.71^△△	767.45±30.90	7.30±1.80^△	62.32±2.86^△△
High dose of VAP	81.82±3.71^△△	673.85±26.89^△△	9.40±1.30^△△	67.33±1.83^△△

Group	SOD[λ_B/(U·mg^－1)]	MDA[m_B/(nmol·mg^－1)]
Normal control	11.97±1.98	1.23±0.11
MCI	4.00±1.48^*	3.10±0.54^*
Piracetam	7.86±1.81^△	1.48±0.12^△
Low dose of VAP	4.22±2.46	2.36±0.25
High dose of VAP	5.95±1.97^△	1.87±0.25^△

Group	Keap1	Nrf2	HO-1
Normal control	0.47±0.03	0.51±0.02	0.97±0.02
MCI	0.85±0.03^**	0.27±0.01^**	0.70±0.03^*
Piracetam	0.56±0.02^△	0.47±0.01^△	0.81±0.02^△
Low dose of VAP	0.71±0.02^△	0.30±0.02^△	0.86±0.02^△
High dose of VAP	0.67±0.03^△	0.36±0.02^△	0.91±0.02^△

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Improvement effects of pilose antler polypeptide on learning and memory abilities in rats with mild cognitive impairment and their mechanisms of regulating Keap1/Nrf2 /HO-1 signaling pathway

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