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化痰通络汤对胶原诱导关节炎大鼠滑膜组织血管内皮生长因子受体 2 表达的影响。

Effects of Huatan Tongluo decoction on vascular endothelial growth factor receptor 2 expression in synovial tissues of rats with collagen-induced arthritis.

机构信息

Department of Rheumatology, Xiamen Hospital of Traditional Chinese Medicine, the Eighth Affiliated Hospital of Beijing University of Chinese Medicine, Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Xiamen 361009, China.

School of Pharmaceutical Sciences, Xiamen University, Xiamen 361009, China.

出版信息

J Tradit Chin Med. 2019 Apr;39(2):191-198.

PMID:32186041
Abstract

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.

摘要

目的

观察化痰通络汤对胶原诱导性关节炎大鼠的治疗作用及可能机制。

方法

40 只 SPF 级 Wistar 大鼠,随机抽取 10 只为空白对照组(1 组),其余大鼠于尾根部及背部皮内多点注射Ⅱ型牛胶原蛋白乳剂,首次免疫后 7 天加强免疫 1 次,建立胶原诱导性关节炎(CIA)模型大鼠后,随机分为 3 组(n=10),分别灌胃生理盐水、模型(生理盐水)、雷公藤多苷(阳性对照,7.81 mg/kg)、化痰通络汤(7.5 g/kg),连续给药 30 天,观察大鼠体质量、踝关节肿胀度及关节炎指数的变化,治疗 30 天后处死大鼠,HE 染色观察关节滑膜组织病理学改变,彩色多普勒超声检测左踝关节滑膜增生及血管翳形成情况,免疫组化法检测血管内皮生长因子(VEGF)、血管内皮生长因子受体 2(VEGFR2)蛋白的表达,实时荧光定量聚合酶链反应(PCR)检测 VEGF/VEGFR2mRNA 的表达。

结果

与模型组比较,阳性对照组(P<0.05)和化痰通络汤组(P<0.01)关节炎指数明显降低,雷公藤多苷和化痰通络汤均可减轻 CIA 大鼠关节内的血管翳形成和滑膜增生,降低 VEGF mRNA 及 VEGFR2 蛋白和 mRNA 的表达(P<0.05)。

结论

化痰通络汤可能通过下调滑膜组织 VEGF、VEGFR2 的表达,抑制血管翳和滑膜增生,从而缓解 CIA 大鼠的关节炎症状。

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