机构地区:[1]河南大学第一附属医院骨科,河南省开封市475001
出 处:《中国组织工程研究》2023年第31期5002-5008,共7页Chinese Journal of Tissue Engineering Research
基 金:开封市科技发展计划项目(2003028),项目负责人:陈有。
摘 要:背景:黄芪多糖治疗骨关节炎具有一定的作用,Toll样受体4/核因子κB通路在膝骨关节炎发病机制中发挥重要作用。目的:探讨黄芪多糖对膝骨关节炎的干预作用及其机制。方法:40只SD大鼠随机分为对照组、模型组、黄芪多糖低剂量组、黄芪多糖高剂量组和脂多糖组(n=8),除对照组之外,其余各组均建立膝骨关节炎模型。造模成功1周后,黄芪多糖低、高剂量组分别向大鼠膝关节腔内注射质量浓度为0.1,0.5 g/L的黄芪多糖生理盐水溶液0.2 mL,脂多糖组注射0.5 g/L黄芪多糖0.2 mL+500μg/kg脂多糖0.2 mL;模型组和对照组同法注射等量生理盐水;均3 d注射1次,干预6周。干预结束后,苏木精-伊红、番红O-固绿染色观察软骨、滑膜组织病理学变化,采用Mankin’s评分和国际骨关节炎研究协会评分进行评估;ELISA法检测滑膜组织中白细胞介素1β、白细胞介素6、肿瘤坏死因子α、一氧化氮、丙二醛、超氧化物歧化酶表达水平;Western blot检测软骨组织中聚集蛋白聚糖、Ⅱ型胶原、基质金属蛋白酶3及核因子κB p65、Toll样受体4、MyD88表达。结果与结论:①与模型组相比,黄芪多糖低、高剂量组的Mankin’s评分、国际骨关节炎研究协会评分、白细胞介素1β、白细胞介素6、肿瘤坏死因子α、一氧化氮、丙二醛、基质金属蛋白酶3水平及核因子κB p65、Toll样受体4、MyD88表达均显著降低,聚集蛋白聚糖、Ⅱ型胶原表达及超氧化物歧化酶活性均显著升高(P<0.05),且黄芪多糖高剂量组均较低剂量组作用更明显(P<0.05);②与黄芪多糖高剂量组比,脂多糖组Mankin’s评分、国际骨关节炎研究协会评分、白细胞介素1β、白细胞介素6、肿瘤坏死因子α、一氧化氮、丙二醛、基质金属蛋白酶3水平及核因子κB p65、Toll样受体4、MyD88表达均显著升高,聚集蛋白聚糖、Ⅱ型胶原表达及超氧化物歧化酶活性均显著降低(P<0.05);③提示BACKGROUND:Astragalus polysaccharide has a certain role in the treatment of arthritis,and abnormal Toll-like receptor 4/nuclear factorκB pathway plays an important role in the pathogenesis of knee osteoarthritis.OBJECTIVE:To investigate the effect of astragalus polysaccharide on osteoarthritis and its mechanism.METHODS:Forty SD rats were randomly divided into control group(the same volume of normal saline),model group(the same volume of normal saline),astragalus polysaccharide low-dose group(0.2 mL of 0.1/L astragalus polysaccharide intervention),astragalus polysaccharide high-dose group(0.2 mL of 0.5 g/L astragalus polysaccharide intervention),and lipopolysaccharide group(0.2 mL of 0.5 g/L astragalus polysaccharide+0.2 mL of 500μg/kg lipopolysaccharide).Interventions in each group began at 1 week after modeling,once every 3 days,for 6 continuous weeks.After intervention,histopathological changes of the cartilage and synovial membrane were observed by hematoxylin-eosin staining and saffron O-solid green staining.Mankin’s score and Osteoarthritis Research Society International score were performed for histological evaluation.The levels of interleukin-1β,interleukin-6,tumor necrosis factor-α,nitric oxide,malondialdehyde,and superoxide dismutase in synovial tissue were detected by ELISA.The protein levels of Aggrecan,collagen type Ⅱ,matrix metalloproteinase 3,nuclear factor-κB p65,Toll-like receptors 4 and myeloid differentiation factor 88 in cartilage tissue were detected by western blot assay.RESULTS AND CONCLUSION:(1)Compared with the model group,the Mankin’s score,Osteoarthritis Research Society International score,the levels of interleukin-1β,interleukin-6,tumor necrosis factor-α,nitric oxide,malondialdehyde,and matrix metalloproteinase 3,and the expressions of nuclear factorκB p65,Toll-like receptors 4,and myeloid differentiation factor 88 were significantly decreased in the astragalus polysaccharide low-and high-dose groups,while the expression levels of Aggrecan,collagen type Ⅱ,and superoxide
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