首页|基于Hedgehog信号通路探讨四神煎对膝骨关节炎大鼠关节软骨的保护作用

基于Hedgehog信号通路探讨四神煎对膝骨关节炎大鼠关节软骨的保护作用

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目的 探究四神煎对膝骨关节炎大鼠关节软骨的保护作用及其可能的作用机制.方法 40只大鼠分为假手术组、模型组、四神煎低剂量组及高剂量组,每组10只.分组后灌胃给药,每天1次,连续6周.采用HE染色检查膝关节组织形态学变化;采用Micro-CT检测软骨下骨的结构情况并对骨小梁形态学参数进行分析;用qPCR分析各组软骨组织中音猬因子(Shh)、神经胶质瘤相关癌基因同源物1(Gli1)及II型胶原蛋白(Collagen II)的mRNA表达变化.结果 HE染色结果表明,模型组整体染色欠均匀,关节软骨表面破坏明显,且具有明显裂隙,软骨层变薄,软骨数量减少,软骨细胞分布排列紊乱,各层次界限不清晰,潮线明显不规则紊乱,而四神煎低剂量及高剂量组较模型组均有改善.Micro-CT显示模型组关节面破坏严重伴骨赘形成,软骨下骨骨量明显减少,四神煎低剂量及高剂量组均较之改善;与模型组比较,四神煎高剂量组大鼠骨小梁数量(Tb.N)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、软骨组织中Collagen II的mRNA表达量显著增加(P<0.05),Shh、Gli1的mRNA表达量明显下降(P<0.001).结论 四神煎对膝骨关节炎大鼠关节软骨具有保护作用,其作用机制可能与抑制Hedgehog信号通路调控Collagen II的表达有关.
Exploration of Protective Effect of Sishen Decoction on Articular Cartilage in Rats with Knee Osteoarthritis via Hedgehog Signal Pathway
Objective To explore the potential protective effects of Sishen Decoction on articular cartilage in a rat model of knee osteoarthritis and elucidate the underlying mechanism.Methods Forty rats were randomly divided into four groups:sham operation group(SOG),model group(MG),low-dose group(LDG)of Sishen Decoction and high-dose group(HDG)of Sishen Decoction,with 10 rats in each group.Intragastric administration was conducted once daily over a continuous six-week period.Next,HE staining was employed to examine the morphological changes in knee joint tissues.Micro-CT was used to assess the structural conditions of subchondral bone and analyze morphological parameters of bone trabeculae.Additionally,qPCR was applied to analyze the changes in mRNA expression of Shh,Gli1 and collagen II in cartilage tissues of each group.Results The results of HE staining revealed that MG exhibited overall uneven staining,significant damage to the articular cartilage surface with evident fissures,thinning of the cartilage layer,reduced cartilage quantity,disordered distribution and arrangement of chondrocytes,unclear boundaries of each layer and conspicuous irregularities in the tidemark.In contrast,LDG and HDG showed certain improvement compared to MG.Micro-CT demonstrated severe joint surface damage accompanied by formation of osteophyte in MG and marked reduction in subchondral bone mass,which was notably ameliorated in LDG and HDG.Compared to MG,the rats in HDG exhibited significant increases in bone trabecular number(Tb.N),bone volume fraction(BV/TV),trabecular thickness(Tb.Th)and the mRNA expression of collagen II in cartilage tissue(P<0.05),while the mRNA expression levels of Shh and Gli1 significantly decreased(P<0.001).Conclusion Sishen Decoction exhibits protective effects on the articular cartilage of rats with knee osteoarthritis,and its mechanism of action may be related to the inhibition of the Hedgehog signal pathway and regulation of the expression of collagen II.

Sishen Decoctionknee osteoarthritisHedgehog signal pathwayarticular cartilage

朱凯、李嘉程、许波

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上海中医药大学附属岳阳中西医结合医院,上海,200437

山东中医药大学第一临床医学院,山东 济南 250014

四神煎 膝骨关节炎 Hedgehog信号通路 关节软骨

山东省医药卫生科技发展计划项目山东省自然科学基金联合基金项目

202004071045ZR202208300064

2024

食品与药品
山东省生物药物研究院

食品与药品

CSTPCD
影响因子:0.537
ISSN:1672-979X
年,卷(期):2024.26(3)
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