益气养血方对膝骨关节炎模型大鼠血清Wnt4和WIF1的影响

Effect of Yiqi Yangxue Fang(益气养血方)on Wnt4 and WIF1 in Serum of Rats with Knee Osteoarthritis

目的:探讨益气养血方对膝骨关节炎大鼠血清Wnt4、WIF1水平及膝关节软骨组织的影响,揭示其治疗骨关节炎的部分机制。方法:将70只SD大鼠随机分为益气养血方低、中、高剂量组,阳性对照组,模型对照组,空白对照组及假手术组,每组10只。除空白对照组和假手术组外,其余各组大鼠采用改良Hulth法构建膝骨关节炎模型;假手术组仅切开关节囊,不切断韧带和半月板。造模成功后,益气养血方低、中、高剂量组分别予益气养血方1.89 g·kg^(-1)·d^(-1)、3.78 g·kg^(-1)·d^(-1)、7.56 g·kg^(-1)·d^(-1)灌胃,阳性对照组给予双氯芬酸钠肠溶片混悬液4 mg·kg^(-1)·d^(-1)灌胃,模型对照组、假手术组给予生理盐水2.5 mL·d^(-1)灌胃,空白对照组不予任何药物。给药8周后,腹主动脉取血,检测血清中Wnt4、WIF1的含量;取右膝关节,HE染色,并进行病理评分。结果:与模型对照组比较,益气养血方各剂量组及阳性对照组病理评分降低(P<0.05);与空白对照组、假手术组比较,模型对照组大鼠血清中Wnt4水平升高、WIF1水平降低(P<0.05);与模型对照组比较,益气养血方中、高剂量组大鼠血清中Wnt4水平降低,WIF1水平升高(P<0.05或P<0.01);与阳性对照组比较,益气养血方中、高剂量对WIF1的上调作用更为明显(P<0.05)。结论:益气养血方能延缓骨关节炎软骨退变,保护关节软骨,其机制可能与下调Wnt4的表达,上调WIF1的水平,抑制关节软骨退变相关。

Objective：To investigate the effect of Yiqi Yangxue Fang （ 益气养血方 ） on Wnt4 and WIFlin serum of rats with knee osteoarthritis,to reveal its mechanism in the treatment of osteoarthritis. Methods：Seventy SD rats were randomly divided into low, middle and high dose groups of Yiqi Yangxue Fang,a positive control group,a model control group,a blank control group and a sham operation group,10 rats in each group.Except for the blank control group and the sham operation group,the knee osteoarthritis models were established by modified Hulth method in the other groups.Only the joint capsule was cut open in the sham operation group,and the ligaments and menisci were not cut off.After modeling,rats in the low, medium and high dose group were respectively given intragastric administration of 1.89 kg^-1·d^-1d-1,3.78 g·kg^-1·d^-1 and 7.56 g kg^-1·d^-1 of Yiqi Yangxue Fang.The positive control group was given intragastric administration of 4 mg ^-1·d^-1 of Diclofenac Sodium Enteric-coated Tablets suspension.The model control group and the sham operation group were given 2.5 mL · d^-1 of normal saline.The blank control group wasn＇t given any drug.After 8 weeks of administration,the blood of abdominal aorta was collected to detect he contents of Wnt4 and WlF1 in serum.The right knee joint was taken for HE staining and pathological score.Results：Compared with the model group,the pathological scores of each group ofYiqi Yangxue Fang and the positive control group decreased （ P 〈 0.05 ） .Compared with the sham operation group and the blank control group,the level of Writ4 increased and the level of WIF 1 decreased in the model control group （ P 〈 0.05 ） .Compared with the model control group,the level of Wnt4 could be lowered and the level of WIF1 could be increased in the medium and high dose group ofYiqi Yangxue Fang （ P 〈 0.05 or P 〈 0.01 ） . Compared with the positive control group,the medium and high dose of Yiqi Yangxue Fang are more obviously to up-regulate the level of WIF1 （P 〈 0.05 ） .Conelusion：Yiqi Yangxue Fang can delay cartilage degeneration and protect articular cartilage,and its mechanism may be related to down regulation of Wnt4,up regulation of WIF1 level and inhibition of articular cartilage degeneration.