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不同剂量金雀异黄酮对骨关节炎模型大鼠关节疼痛、炎症的抑制作用 被引量:6

Inhibitory effects of different doses of genistein on joint pain and inflammation in osteoarthritis model rats
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摘要 背景:金雀异黄酮是一种大豆制品衍生物,具有预防骨质疏松和抑制癌症的作用,其对骨关节炎的作用目前尚无相关报道。目的:分析不同剂量金雀异黄酮对骨关节炎的效果并探讨其机制。方法:采用木瓜蛋白酶法建立雄性Wistar大鼠右膝骨关节炎模型,分5组干预:低、中、高剂量组分别灌胃给予4.5,9,18 mg/(kg·d)的金雀异黄酮,阳性对照组灌胃给予15 mg/(kg·d)的双氯芬酸钠,对照组灌胃给予纯净水,连续给药35 d。给药后第7,14,21天检测右膝膝关节直径;给药后第1,3,5周检测右膝关节液中炎性因子水平。分别于雄性Wistar大鼠皮肤表面涂纯净水、金雀异黄酮胶体和0.8%甲醛,建立皮肤刺激模型,观察皮肤出现红肿及皮疹情况。采用醋酸法建立雄性Wistar大鼠疼痛翻滚模型,醋酸注射3 min后分组干预,干预方式同骨关节模型,记录前20 min与后20 min大鼠肢体翻滚次数,判断止痛效果。实验方案经南方医科大学动物实验伦理委员会批准。结果与结论:①相同时间点内,中、高剂量组与阳性对照组膝关节直径小于对照组(P<0.05),前3组间比较差异无显著性意义(P>0.05);②相同时间点内,中、高剂量组与阳性对照组基质金属蛋白酶3、白细胞介素6、白细胞介素1β水平均低于对照组(P<0.05),前3组间比较差异无显著性意义(P>0.05);③金雀异黄酮凝胶涂于大鼠皮肤表面后皮肤无皮疹及红肿;④前20 min与后20 min内,9,18 mg/kg的金雀异黄酮可缓解大鼠疼痛,其止痛效果和双氯芬酸钠无明显差别;⑤结果表明,金雀异黄酮对皮肤无刺激性,在一定剂量范围内具有止痛、抗炎、消肿和抗骨关节炎的功效。 BACKGROUND:Genistein is a soy product derivative that can prevent osteoporosis and inhibit cancer.There is no relevant report on its role in osteoarthritis.OBJECTIVE:To study the effects of different doses of genistein on osteoarthritis and to explore its mechanism.METHODS:A model of right knee osteoarthritis was established in male Wistar rats by using papain method.The experiment was divided into five groups:low,medium and high dose groups were administered with 4.5,9,and 18 mg/(kg•d)genistein,respectively;a positive control group was given 15 mg/(kg•d)diclofenac sodium by gavage;and a control group was given pure water.Administration in each group was kept for 35 continuous days.The knee joint diameter of the right knee was measured on the 7th,14th,and 21st day after administration.At the 1st,3rd,and 5th week after administration,the levels of inflammatory factors in the right knee joint fluid were measured.Pure water,genistein colloid and 0.8%formaldehyde were separately applied to the skin surface of male Wistar rats to establish a skin irritation model.Redness and rash on the skin were then observed.The painful tumbling model of male Wistar rats was established by acetic acid method.The intervention method was the same as the knee osteoarthritis model.The number of limb tumbling in the rats within the first and the last 20 minutes was recorded to assess the analgesic effect.Ethic approval was obtained from the Animal Experiment Ethics Committee of Southern Medical University.RESULTS AND CONCLUSION:At the same time point,the knee joint diameter of the middle and high dose groups and the positive control group was smaller than that of the control group(P<0.05),and there was no significant difference between the first three groups(P>0.05).At the same time point,the levels of matrix metalloproteinase-3,interleukin-6 and interleukin-1βwere lower in the middle and high dose groups and the positive control group than in the control group(P<0.05),and there was no significant difference between the first three groups(P>0.05).Genistein gel did not result in induce rash and redness on the surface of the rat skin.In the first and the last 20 minutes,9 and 18 mg/kg genistein could alleviate pain in rats,and its analgesic effect was similar to that of diclofenac sodium.All these findings indicate that genistein is not irritating to the skin and within a certain dose range,genistein can relieve pain and have anti-inflammatory,anti-swelling and anti-osteoarthritis effects.
作者 曾小云 张丽容 Zeng Xiaoyun;Zhang Lirong(General Department of People’s Hospital of Longhua District,Shenzhen 518109,Guangdong Province,China)
出处 《中国组织工程研究》 CAS 北大核心 2020年第35期5607-5612,共6页 Chinese Journal of Tissue Engineering Research
关键词 软骨 骨关节炎 因子 实验 动物 bone cartilage rat osteoarthritis factor experiment animal
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