Effects of Huatan Tongluo decoction on vascular endothelial growth factor receptor 2 expression in synovial tissues of rats with collagen-induced arthritis
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摘要
OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.
OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.
OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.
引文
1 Smets P,Devauchelle-Pensec V,Rouzaire PO,Pereira B,Andre M,Soubrier M.Vascular endothelial growth factor levels and rheumatic diseases of the elderly.Arthritis Res Ther 2016;18(1):283.
2 Kelly S,Bombardieri M,Humby F,et al.Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis:an observational study.Arthritis Res Ther2015;17:58.
3 Azizi G,Boghozian R,Mirshafiey A.The potential role of angiogenic factors in rheumatoid arthritis.Int J Rheum Dis 2014;17(4):369-383.
4 Qiu MS,Chen JC,Zhang YY,Xu ZX,Jiang FP,Peng HC.Effect of Huatan Tongluo Fang on collagen-induced arthritis in rats.Beijing Zhong Yi Yao Da Xue Xue Bao2012;35(2):121-124.
5 Zhang YY,Qiu MS,Chen JC,Zhang YY.Clinical observation of Huatan Tongluo Fang on patients with Rheumatoid Arthritis.Zhong Yi Yao Tong Bao 2012;12(1):45-48.
6 National pharmacopoeia commission.Chinese pharmacopoeia(part I).Beijing:China Medical Science And Technology Press,2015:261.
7 Yi M,Deng JG,Hao EW,Ye XI,Wang JS,Du ZC.Pharmacodynamic effects of Persicae Semen extract on blood circulation disorder of rats induced by different symtoms.Zhong Cao Yao 2013;44(7):858-862.
8 Dong HL,Guo SX,Wang CL,Yang JS,Xiao PG.Advances in studies on chemical constituents in plants of Pseudobulbus Cremastrae seu Pleiones and their pharmacological activities.Zhong Cao Yao 2007;38(11):1734-1738.
9 Tu S,Hu Y,Zeng K,Zhang M,Lai X,Zhang WC.Effects of triptolide on the expression and activity of NF-kappaBin synovium of collagen-induced arthritis rats.Hua Zhong Ke Ji Da Xue Xue Bao 2005;25(5):543-545.
10 Song HX,Wang QS.High-frequency ultrasound imaging of collagen-induced arthritis in rats.Nan Fang Yi Ke Da Xue Xue Bao 2013;33(12):1766-1770.
11 Sreerangaiah D,Grayer M,Fisher BA,Ho M,Abraham S,Taylor PC.Quantitative power Doppler ultrasound measures of peripheral joint synovitis in poor prognosis early rheumatoid arthritis predict radiographic progression.Rheumatology 2016;55:89-93.
12 Semerano L,Duvallet E,Belmellat N,et al.Targeting VEGF-A with a vaccine decreases inflammation and joint destruction in experimental arthritis.Angiogenesis 2016;19(1):39-52.
13 Smolen JS,Aletaha D,Barton A,et al.Rheumatoid arthritis.Nature reviews.Disease Primers 2018;4:18001.
14 Gonzalo-Gil E,Galindo-Izquierdo M.Role of transforming growth factor-beta(TGF)beta in the physiopathology of rheumatoid arthritis.Reumatol Clin 2014;10(3):174-179.
15 Chen GJ,Forough R.Fibroblast growth factors,fibroblast growth factor receptors,diseases,and drugs.Recent Pat Cardiovasc Drug Discov 2016;1(2):211-224.
2 Kelly S,Bombardieri M,Humby F,et al.Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis:an observational study.Arthritis Res Ther2015;17:58.
3 Azizi G,Boghozian R,Mirshafiey A.The potential role of angiogenic factors in rheumatoid arthritis.Int J Rheum Dis 2014;17(4):369-383.
4 Qiu MS,Chen JC,Zhang YY,Xu ZX,Jiang FP,Peng HC.Effect of Huatan Tongluo Fang on collagen-induced arthritis in rats.Beijing Zhong Yi Yao Da Xue Xue Bao2012;35(2):121-124.
5 Zhang YY,Qiu MS,Chen JC,Zhang YY.Clinical observation of Huatan Tongluo Fang on patients with Rheumatoid Arthritis.Zhong Yi Yao Tong Bao 2012;12(1):45-48.
6 National pharmacopoeia commission.Chinese pharmacopoeia(part I).Beijing:China Medical Science And Technology Press,2015:261.
7 Yi M,Deng JG,Hao EW,Ye XI,Wang JS,Du ZC.Pharmacodynamic effects of Persicae Semen extract on blood circulation disorder of rats induced by different symtoms.Zhong Cao Yao 2013;44(7):858-862.
8 Dong HL,Guo SX,Wang CL,Yang JS,Xiao PG.Advances in studies on chemical constituents in plants of Pseudobulbus Cremastrae seu Pleiones and their pharmacological activities.Zhong Cao Yao 2007;38(11):1734-1738.
9 Tu S,Hu Y,Zeng K,Zhang M,Lai X,Zhang WC.Effects of triptolide on the expression and activity of NF-kappaBin synovium of collagen-induced arthritis rats.Hua Zhong Ke Ji Da Xue Xue Bao 2005;25(5):543-545.
10 Song HX,Wang QS.High-frequency ultrasound imaging of collagen-induced arthritis in rats.Nan Fang Yi Ke Da Xue Xue Bao 2013;33(12):1766-1770.
11 Sreerangaiah D,Grayer M,Fisher BA,Ho M,Abraham S,Taylor PC.Quantitative power Doppler ultrasound measures of peripheral joint synovitis in poor prognosis early rheumatoid arthritis predict radiographic progression.Rheumatology 2016;55:89-93.
12 Semerano L,Duvallet E,Belmellat N,et al.Targeting VEGF-A with a vaccine decreases inflammation and joint destruction in experimental arthritis.Angiogenesis 2016;19(1):39-52.
13 Smolen JS,Aletaha D,Barton A,et al.Rheumatoid arthritis.Nature reviews.Disease Primers 2018;4:18001.
14 Gonzalo-Gil E,Galindo-Izquierdo M.Role of transforming growth factor-beta(TGF)beta in the physiopathology of rheumatoid arthritis.Reumatol Clin 2014;10(3):174-179.
15 Chen GJ,Forough R.Fibroblast growth factors,fibroblast growth factor receptors,diseases,and drugs.Recent Pat Cardiovasc Drug Discov 2016;1(2):211-224.