山茱萸多糖对难治性癫痫幼鼠行为学和海马组织中多药耐药基因1b及主穹隆蛋白表达的影响

doi:10.13481/j.1671-587X.20210314

Abstract

Abstract:

Objective： To investigate the effects of Cornus officinalis polysaccharide on the behavior and the multidrug resistance gene 1b（MDR1b） and main vault protein （MVP） in hippocampus tissue of the refractory epilepsy （RE） young rats， and to clarify their mechanisms.

Methods

A total of 40 young rats were used to establish the RE models and then they were randomly divided into model group （n=8），low dose of Cornus officinalis polysaccharide group （n=9），high dose of Cornus officinalis polysaccharide group（n=10）， and positive control group （n=10）；sham operation group was set up at the same time（n=10）. The young rats in low and high doses of Cornus officinalis polysaccharide groups were given 0.14 and 0.56 g·kg^－1Cornus officinalis polysaccharide by gavage，the young rats in positive control group were given 154 mg·kg^－1 lamotrigine， and the young rats in control group and model group were given the same amount of normal saline. The epoleptic behavioral changes of the young rats in various groups were observed；the patholomorphology of hippocampus tissue of the young rats in various groups were observed by HE staining；the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） of the young rats in various groups were detected by ELISA method， and expression levels of nuclear factor-κB （NF-κB）， MDR1b， and MVP mRNA and proteins in hippocampus tissue of the young rats in various groups were detected by RT-qPCR and Western blotting methods.

Results

Compared with sham operation group， the total number of seizures of the young rats in model group was increased（P<0.05），the total duration was prolonged（P<0.05）， the serum levels of TNF-α and IL-1β were increased（P<0.05），and the expression levels of NF-κB， MDR1b， and MVP mRNA and proteins in hippocampus tissue of the young rats were increased （P<0.05）. Compared with model group， the total number of seizures of the young rats in low and high doses of Cornus officinalis polysaccharide groups and positive control group was decreased（P<0.05），the total duration was shortened（P<0.05）， the serum levels of TNF-α and IL-1β were decreased （P<0.05）， and the expression levels of MDR1b， MVP mRNA and proteins in hippocampus tissue of the young rats were decreased （P<0.05）.The HE staining results showed that the morphology and structure of the cells in hippocampus area of the young rats in sham operation group were normal； the cells in hippocampus area of the young rats in model group were arranged disorderly， a large number of cells showed vacuole-like changes， and a large number of nuclear ruptures and nuclear pyknosis were seen； the cells in hippocampus area of the young rats in low and high doses of Cornus officinalis polysacharide groups and positive control group were arranged neatly and the cell outline was clear， with a small amount of vacuolar degeneration， nuclear rupture， and nuclear pyknosis.

Conclusion

Cornus officinalis polysaccharide can improve the seizure behavior of RE young rats， and its mechanism may be related to the inhibition of MDR1b and MVP mRNA and protein expressions.

Key words: refractory epilepsy, Cornus officinalis polysaccharide, multidrug resistance gene 1b, main vault protein, nuclear factor-κB

CLC Number:

R742.1

Xiulan YE, Ming LI, Zhaojian WANG, Haiyan ZHAO, Jianning MA, Jing LIU, Yi ZHENG, Shunqing LI, Yu ZHANG. Effects of Cornus officinalis polysaccharide on behavior and multidrug resistance gene 1b and major vault protein expressions in hippocampus tissue of refractory epilepsy young rats[J].Journal of Jilin University(Medicine Edition), 2021, 47(3): 644-651.

Figures/Tables 7

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Primer	Sequence
NF-κB	F:5'-TGTTGAGGATGTTACGTAGATGTA-3'
NF-κB	R:5'-TGAATGTTGAGTTGTACATTCCGG-3'
MDR1b	F:5'-GTGAGTTATTGAGCCGATTAGATTA-3'
MDR1b	R:5'-GTAGTCTATTGCACATGATTACATGT-3'
MVP	F:5'-GTATCTAGGCGCTAGATGTTATATGAT-3'
MVP	R:5'-GTGAGTGCGGTTATAGACTAAGTGC-3'
GAPDH	F:5'-GTTTCAAGGCGTAGATGTGTTATGAT-3'
GAPDH	R:5'-ATGAGTGCGATTATAGATCAAGTGC-3'

Group	n	Total number of attack	Total duration of seizure (t/min)
Sham operation	10	0.00±0.00	0.00±0.00
Model	8	50.12±7.25^*	258.31±35.12^*
Cornus officinalis polysaccharide
Low dose	9	36.23±5.89^△	89.31±12.65^△#
High dose	10	17.65±2.12^△#	180.16±20.31^△
Positive control	10	18.12±2.18^△#	84.31±11.25^△#
F		191.259	253.780
P		<0.01	<0.01

Group	n	TNF-α	IL-1β
Sham operation	10	100.36±12.03	75.21±9.21
Model	8	231.45±25.44^*	135.26±15.13^*
Cornus officinalis polysaccharide
Low dose	9	196.32±21.45^△	113.44±14.12^△
High dose	10	151.16±16.21^△#	94.35±11.10^△#
Positive control	10	150.35±17.12^△#	92.16±10.25^△#
F		64.884	32.541
P		<0.01	<0.01

Group	n	NF-κB	MDR1b	MVP
Sham operation	10	0.18±0.02	0.11±0.03	0.13±0.02
Model	8	0.51±0.07^*	0.45±0.05^*	0.49±0.06^*
Cornus officinalis polysaccharide
Low dose	9	0.40±0.05^△	0.33±0.07^△	0.37±0.07^△
High dose	10	0.29±0.04^△#	0.21±0.04^△#	0.25±0.03^△#
Positive control	10	0.28±0.04^△#	0.22±0.04^△#	0.26±0.04^△#
F		68.666	67.035	76.411
P		<0.01	<0.01	<0.01

Group	n	NF-κB	MDR1b	MVP
Sham operation	10	0.15±0.03	0.09±0.01	0.10±0.02
Model	8	0.49±0.06^*	0.43±0.07^*	0.47±0.05^*
Cornus officinalis polysaccharide
Low dose	9	0.38±0.05^△	0.31±0.06^△	0.35±0.06^△
High dose	10	0.24±0.03^△#	0.18±0.04^△#	0.22±0.03^△#
Positive control	10	0.22±0.04^△#	0.17±0.03^△#	0.21±0.05^△#
F		91.720	76.949	94.265
P		<0.01	<0.01	<0.01

Effects of Cornus officinalis polysaccharide on behavior and multidrug resistance gene 1b and major vault protein expressions in hippocampus tissue of refractory epilepsy young rats

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