摘要
目的研究金雀异黄素对Ⅱ型胶原诱导型关节炎大鼠促炎和抗炎因子分泌的影响。方法建立Ⅱ型胶原诱导型关节炎大鼠模型,通过50、100和200μm的金雀异黄素治疗,以0.1 mg/mL每周甲氨蝶呤(MTX)作为阳性对照,治疗后每周检测Ⅱ型胶原诱导型关节炎大鼠关节炎指数评分和后肢容积,第5周取膝关节进行关节滑膜组织病理检测;取静脉血分离出血清后,用酶联免疫吸附试验检测各组大鼠血清中白细胞介素-4(IL-4)、IL-6、IL-8、IL-10、转化生长因子-β1(TGF-β1)、淋巴毒素-α的水平。结果关节炎指数评分、后肢容积以及关节滑膜组织病理结果显示造模成功。模型组大鼠血清中的炎症因子IL-6、IL-8和淋巴毒素-α的表达水平明显高于空白对照组(P<0.05);金雀异黄素能下调IL-6、IL-8、淋巴毒素-α的分泌,200μm金雀异黄素对IL-6、IL-8的抑制作用与MTX相当,而各金雀异黄素治疗组对淋巴毒素-α的抑制作用均弱于MTX。模型组大鼠血清中的细胞因子IL-4、IL-10、TGF-β1的表达水平低于空白对照组(P<0.05);金雀异黄素能上调IL-4、IL-10、TGF-β1的分泌。100μm金雀异黄素对IL-4的上调作用与MTX相当;200μm金雀异黄素对IL-10的促进作用与MTX相当,对TGF-β1的上调作用强于MTX。结论金雀异黄素抑制Ⅱ型胶原诱导型关节炎大鼠炎症因子的释放,促进抗炎因子的表达,改善关节炎大鼠滑膜炎症。
Objective To investigate the effect of genistein(gen) on the secretion of cytokines in rats with collagen Ⅱ induced arthritis( CIA). Methods The CIA model rats were given different concentration(50,100 and200 μm)of gen treatment,and MTX(0. 1 mg /mL per week) as positive control by contrast,the rats were scored with the arthritis index(AI) and hind paw swelling once a week. After 5 weeks' treatment,the rats were sacrificed,and the knee joints were harvested for pathological examination,and serum were immediately separated from venous blood. The serum concentrations of interleukin-4(IL-4),IL-6,IL-8,IL-10,TGF-β1 and LT-α were determined with enzyme-linked immunosorbent assay(ELISA). Results The results of AI score,hind paw swelling,and pathological detection indicated that the model of CIA rats was constructed successfully. The serum level of IL-6,IL-8,LT-α in the CIA model group was significantly higher than those of control group(P〈0. 05),while Gen could down-regulate the secretion of IL-6,IL-8 and LT-α,the result also showed that Gen at high-dose had the similar inhibition of the secretion of IL-6,IL-8 to MTX group,and the inhibition of LT-α in all Gen treatment groups were weaker than those of MTX group. The serum level of cytokines IL-4,IL-10 and TGF-β1 in CIA model group was significantly lower than those in control group(P〈0.05),Gen could up-regulate the secretion of IL-4,IL-10 and TGF-β1,Gen moderate-dose group have the similar up-regulation effect on the secretion of IL-4 as MTX group. The up-regulating effect on TNFβ1 in Gen high doses group was higher than that of MTX group. Conclusion Gen can inhibit the release of inflammatory factors,and increase the expression of anti-inflammatory cytokines in RA,ameliorate the arthromeningitis of CIA rats.
出处
《实用药物与临床》
CAS
2014年第10期1247-1251,共5页
Practical Pharmacy and Clinical Remedies
基金
江苏省高校自然科学基础研究项目课题(07KJD320245)
关键词
金雀异黄素
甲氨蝶呤
CIA
细胞因子
Genistein
Methotrexate
Collagen induced arthritis
Cytokines