薯蓣皂苷对滑膜炎大鼠症状的改善作用和对TLR2-NF-κB信号通路的调节作用及其机制

doi:10.13481/j.1671-587X.20210417

Abstract

Abstract: Objective

To investigate the improvement effect of diosgenin on the symptoms of synovitis rats and the influence in Toll-like receptor 2 （TLR2） - nuclear factor kappaB（NF-κB） signaling pathway， and to elucidate the possible mechanism of diosgenin in the treatment of synovitis.

Methods

The synovitis models were established by intradermal injection of Freund’s complete adjuvant，and the model rats were randomly divided into model group（n=10），positive drug group （indomethacin 10 mg·kg^－1）（n=11）， low dose of diosgenin group （60 mg·kg^－1）（n=12）， and high dose of diosgenin group （120 mg·kg^－1）（n=12）； another 10 healthy rats were set as control group. Joint pain scoreing and water volume methods were used to evaluate the changes of joint pain and swelling on the 3rd， 7th， 14th and 21st days after intervention. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in synovial tissue of the rats in various groups were detected by enzyme-linked immunosorbent assay method. HE staining was used to observe the pathomorphology of synovium tissue of the rats in various groups. Western bloting method was used to detect the expression levels of TLR2， MyD88， NF-κB and p-NF-κB p65 proteins in synovium tissue of the rats in various groups.

Results

Compared with control group， the pain scores of the rats in model group， positive drug group， low dose of diosgenin group and high dose of diosgenin group at different time points were significantly increased P<0.05）， the degrees of toe swelling were significantly increased （P<0.05）， and the levels of TNF-α and IL-1β in synovial tissue were significantly increased （P<0.05）. Compared with model group， the pain scores of the rats in positive drug group， low dose of diosgenin group and high dose of diosgenin group at different time points were significantly decreased （P<0.05）， the degrees of toe swelling were significantly decreased （P<0.05）， and the levels of TNF-α and IL-1β in synovial tissue were significantly decreased （P<0.05）.Compared with positive drug group， the pain scores of the rats in low dose of diosgenin group and high dose of diosgenin group at different time points were significantly increased （P<0.05）， the degrees of toe swelling were significantly increased （P<0.05），and the levels of TNF-α and IL-1β in synovial tissue were significantly increased （P<0.05）. Compared with low dose of diosgenin group， the pain score of the rats in high dose of diosgenin group was significantly decreased（P<0.05）， the degree of toe swelling was significantly decreased （P<0.05）， and the levels of TNF-α and IL-1β in synovial tissue were significantly decreased （P<0.05）. The results of HE staining showed that the synovial tissue of the rats in control group was normal， the cells arranged orderly， without edema， hyperemia and proliferation， and had no inflammatory cell infiltration； the synovial tissue of the rats in model group had serious edema and hyperemia，the synovial cells were disordered and proliferaed， and there was a large number of inflammatory cell infiltration； the hyperemia and edema of the synovial tissue of the rats in low dose of diosgenin group were alleviated， and the cell proliferation was slightly reduced； in positive drug group and high dose of diosgenin group， the synovial tissue was slightly edema and congestive， the cells were regularly arranged，and there was small amount of inflammatory cell infiltration and rare proliferation. Compared with control group， the expression levels of TLR2， MyD88 and p-NF-κB p65 proteins in synovial tissue of the rats in model group， positive drug group， low dose of diosgenin group and high dose of diosgenin group were significantly increased （P<0.05）；compared with model group， the expression levels of TLR2， MyD88 and p-NF-κB p65 proteins in synovial tissue of the rats in positive drug group， low dose of diosgenin group and high dose of diosgenin group were significantly increased （P<0.05）；compared with positive group， the expression levels of TLR2， MyD88 and p-NF-κB p65 proteins in synovial tissue of the rats in low and high doses of diosgenin groups were significantly increased （P<0.05）； compared with low dose of diosgenin group， the expression levels of TLR2， MyD88 and p-NF-κB p65 proteins in synovial tissue of the rats in high dose of diosgenin group were significantly decreased（P<0.05）.

Conclusion

Diosgenin may improve the symptoms of synovitis rats by inhibiting the TLR2-NF- κB signaling pathway.

Key words: diosgenin, synovitis, Toll-like receptor 2, nuclear factor-κB, inflammatory cytokines

CLC Number:

R285.5

Haojie WU,Minghui ZHANG,Chengzhi HONG. Improvement effect of diosgenin on symptoms of synovitis rats and its reglatory effect on TLR2-NF-κB signaling pathway and mechanism[J].Journal of Jilin University(Medicine Edition), 2021, 47(4): 943-950.

Figures/Tables 6

Tab. 1

Tab. 2

Tab.3

Fig. 1

Tab.4

Fig. 2

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Group	n	Pain score
Group	n	（t/d） 3	7	14	21
Control	10	0.64±0.11	0.66±0.12	0.61±0.14	0.65±0.13
Model	10	10.62±1.23^*	12.98±1.16^*□	14.78±1.45^*□▲	16.69±1.98^*□▲●
Positive drug	11	7.14±0.75^*△	5.01±1.52^*△□	3.58±0.74^*△□▲	1.78±0.35^{*△□▲●}
Diosgenin Low dose	12	9.42±1.27^*△#	8.39±1.58^*△#□	7.39±0.71^*△#□▲	4.74±0.45^{*△#□▲●}
High dose	12	8.25±1.28^*△#O	6.77±1.54^*△#O□	4.94±0.77^*△#O□▲	2.78±0.29^{*△#O□▲●}
F		140.339	115.942	395.789	542.709
P		<0.01	<0.01	<0.01	<0.01

Group	n	Toe swelling degree
Group	n	（t/d） 3	7	14	21
Control	10	0.03±0.01	0.04±0.01	0.02±0.01	0.03±0.01
Model	10	0.75±0.08^*	0.97±0.09^*□	1.45±0.19^*□▲	1.61±0.09^*□▲●
Positive drug	11	0.41±0.05^*△	0.32±0.04^*△□	0.24±0.03^*△□▲	0.12±0.02^{*△□▲●}
Diosgenin Low dose	12	0.61±0.07^*△#	0.48±0.08^*△#□	0.37±0.04^*△#□▲	0.24±0.05^{*△#□▲●}
High dose	12	0.53±0.08^*△#○	0.37±0.04^*△#○□	0.29±0.05^{*△#○□▲}	0.19±0.03^{*△#○□▲●}
F		182.726	326.404	418.313	1 920.000
P		<0.01	<0.01	<0.01	<0.01

Group	n	TNF-α	IL-1β
Control	10	61.22±7.03	5.26±0.24
Model	10	180.39±10.06^*	10.47±0.95^*
Positive drug	11	139.25±11.02^*△	5.31±0.53^*△
Diosgenin Low dose	12	104.34±8.04^*△#	8.44±0.74^*△#
High dose	12	90.29±9.03^*△#○	6.98±0.85^*△#○
F		259.719	99.563
P		<0.01	<0.01

Group	n	TLR2	MyD88	NF-κB	p-NF-κB p65
Control	10	0.24±0.06	0.17±0.04	0.59±0.12	0.05±0.01
Model	10	0.85±0.09^*	0.69±0.07^*	0.58±0.15	0.45±0.08^*
Positive drug	11	0.33±0.04^*△	0.32±0.08^*△	0.60±0.14	0.11±0.02^*△
Diosgenin Low dose	12	0.49±0.08^*△#	0.48±0.09^*△#	0.61±0.12	0.36±0.05^*△#
High dose	12	0.37±0.05^{*△# ○}	0.39±0.11^*△#○	0.59±0.11	0.19±0.03^*△#○
F		41.877	54.856	0.088	151.553
P		<0.01	<0.01	0.986	<0.01

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Improvement effect of diosgenin on symptoms of synovitis rats and its reglatory effect on TLR2-NF-κB signaling pathway and mechanism

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