Li-min WANG, Jing YU, Ye-yu ZHAO, et al. Effect of Xiao Chaihutang on NF-κB Signaling Pathway in Synovial Tissue of CFA Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 44-50.
DOI:
Li-min WANG, Jing YU, Ye-yu ZHAO, et al. Effect of Xiao Chaihutang on NF-κB Signaling Pathway in Synovial Tissue of CFA Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 44-50. DOI: 10.13422/j.cnki.syfjx.20191401.
Effect of Xiao Chaihutang on NF-κB Signaling Pathway in Synovial Tissue of CFA Rats
To observe the expression of tumor necrosis factor receptor-associated death domain (TARDD)
nuclear transcription factor-
κ
B inhibiting protein
α
(I
κ
B
α
)I
κ
B kinase-
α
(IKK
α
) and nuclear transcription factor (NF)-
κ
B p65 protein in the NF-
κ
B signaling pathway of synovial tissues of complete Freund's adjuvant (CFA) rats after treatment with Xiao Chaihutang (XCHT).
Method:
2
In animal experiments
SPF health adult female Wistar rats were used to prepare the CFA animal model of rats with rheumatoid arthritis with Freund's complete adjuvant and cattle Ⅱ collagen type. According to the random number table
the rats were randomly divided into the normal group
the model group
the low-dose XCHT group
the medium-dose XCHT group
the high-dose XCHT group
and the Tripterygium glucosides group. The drugs were given at 7 d after the model was built. Both normal group and model group were given water for injection
and low-dose XCHT group(5.94 g·kg
-1
)
medium-dose XCHT group(11.88 g·kg
-1
)
high-dose XCHT group(23.76 g·kg
-1
)
Tripterygium glucosides group(0.006 3 g·kg
-1
) were given corresponding drugs by gavage for three times a day
2 mL/time. The histopathology of rat ankle joint was observed
and the protein expressions of TARDD
IKK
α
I
κ
B
α
NF-
κ
B p65 in the NF-
κ
B signaling pathway in synovial tissue of CFA rats were detected by Western blot.
Result:
2
With the increase of the dosage of XCHT
the histopathological score of the right posterior ankle joint of the experimental rats was increased. And in the protein expressions of TARDD
IKK
α
I
κ
B
α
NF-
κ
B p65 in NF-
κ
B signaling pathway in Synovial Tissue of CFA rats
compared with the model group
the statistical results of the low-dose XCHT group showed decreased protein expressions (
P
<
0.05) and significant differences. However
the statistical results in the medium-dose XCHT group
the high-dose XCHT group and the tripterygium glucosides group showed decreased protein expression (
P
<
0.01) and significant differences. Compared with the normal group
the histopathological score of the right posterior ankle of the model group was significantly increased(
P
<
0.01)
and the protein expressions of TARDD
IKK
α
I
κ
B
α
NF-
κ
B p65 in the NF-
κ
B signaling pathway were significantly increased (
P
<
0.01). Compared with model group
with the increase of dose of Xiao Chaihutang
histopathologic score of posterior ankle of experimental rats significantly reduced (
P
<
0.01). In rats ankle tissue samples
TARDD
IKK
α
I
κ
B
α
NF-
κ
B p65 key protein expressions in the NF-
κ
B signaling pathway and protein expressions in low-dose XCHT group were obviously lower (
P
<
0.05)
and protein expressions in the medium-dose XCHT group
the high-dose XCHT group and the Tripterygium glucosides group were significantly lower (
P
<
0.01).
Conclusion:
2
This study shows that as the dose of Xiao Chaihutang increases
it could effectively improve synovitis
and suppress the expressions of key proteins in the inflammatory signaling pathway of NF-
κ
B
thereby preventing inflammation and suppressing bone erosion.
关键词
Keywords
references
Smolen J S , Aletaha D , Barton A , et al . Rheumatoid arthritis [J]. Nat Rev Dis Primers , 2018 , 4 : 18001 .
Scott D L . Prognostic factors in early rheumatoid arthritis [J]. Rheumatology (Oxford) , 2000 , 39 ( 1 ): 24 - 29 .
Makarov S S . NF-kappaB in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction [J]. Arthritis Res , 2001 , 3 ( 4 ): 200 - 206 .
Vincenti M P , Coon C I , Brinckerhoff C E . Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1beta-stimulated synovial fibroblasts [J]. Arthritis Rheum , 1998 , 41 ( 11 ): 1987 - 1994 .
Bondeson J , Brennan F , Foxwell B , et al . Effective adenoviral transfer of IkappaB alpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent [J]. J Rheumatol , 2000 , 27 ( 9 ): 2078 - 2089 .
Bond M , Fabunmi R P , Baker A H , et al . Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B [J]. FEBS Lett , 1998 , 435 ( 1 ): 29 - 34 .
Yoshida S , Ono M , Shono T , et al . Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis [J]. Mol Cell Biol , 1997 , 17 ( 7 ): 4015 - 4023 .
Elinav E , Nowarski R , Thaiss C A , et al . Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms [J]. Nat Rev Cancer , 2013 , 13 ( 11 ): 759 - 771 .
Adli M , Merkhofer E , Cogswell P , et al . IKKα and IKKβ each function to regulate NF-κB activation in the TNF-induced/canonical pathway [J]. PLoS One , 2010 , 5 ( 2 ): e9428 .
Hsu H , XIONG J , Goeddel D V . The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation [J]. Cell , 1995 , 81 ( 4 ): 495 - 504 .
Smolen J S , Landewé R , Bijlsma J , et al . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update [J]. Ann Rheum Dis , 2017 , 76 ( 6 ): 960 - 977 .
Bellucci E , Terenzi R , La Paglia G M , et al . One year in review 2016: pathogenesis of rheumatoid arthritis [J]. Clin Exp Rheumatol , 2016 , 34 ( 5 ): 793 - 801 .
LV Q W , ZHANG W , SHI Q , et al . Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial [J]. Ann Rheum Dis , 2015 , 74 ( 6 ): 1078 - 1086 .