摘要
旨在探讨齐墩果酸(oleanolic acid,OLA)对于骨关节炎(osteoarthritis,OA)大鼠肌肉氧化损伤和软骨下骨异常骨重建的作用。选取18只Sprague-Dawley大鼠随机分为3组:对照组(CON组)、模型组(OA组)和齐墩果酸给药组(OLA组)。OA组和OLA组利用前十字韧带切断联合半月板部分切除手术(ACLT+PMMx)建立大鼠膝OA模型,CON组进行假手术。OLA组大鼠每天灌胃50 mg·(kg·d)^(-1) OLA,CON组和OA组灌服等体积含20 mL·L^(-1) Tween 80的无菌生理盐水,连续给药4周后取膝关节、股四头肌和血清样本。利用伸膝发声试验和热敏感试验检测大鼠关节疼痛情况。酶联免疫吸附测定试验检测大鼠肌肉中柠檬酸合酶(citrate synthase,CS)、肌球蛋白重链(myosin heavy chain,MHC)、白细胞介素1(interleukin 1,IL-1)和IL-6的水平,以及大鼠血清中骨钙素(osteocalcin,OCN)和Ⅰ型胶原羧基末端肽(C-terminal typeⅠcollagen telopeptide,CTX-Ⅰ)的水平。免疫印迹法检测肌肉组织Nrf2/NQO1/HO-1通路蛋白表达情况。微型计算机断层扫描(Micro-CT)用于软骨下骨扫描和骨组织显微结构定量分析。结果显示,与OA组比较,OLA可以降低OA疼痛评分(P<0.05),激活肌肉Nrf2/NQO1/HO-1通路,促进肌肉CS和MHC表达,并下调IL-1和IL-6水平(P<0.05)。此外,补充OLA后大鼠软骨下骨的骨体积分数(BV/TV)、骨矿物质密度(BMD)和骨小梁厚度(Tb.Th)显著升高(P<0.05),骨代谢标志物OCN和CTX-Ⅰ表达显著降低(P<0.05)。结果提示,OLA能够抑制OA大鼠关节疼痛反应,通过调控Nrf2/NQO1/HO-1通路抑制OA大鼠肌肉功能障碍,改善OA早期软骨下骨生物力学性能和微结构改变,从而延缓OA大鼠软骨下骨异常骨重建的发生。
We aimed to investigate the effects of oleanolic acid(OLA) on oxidative damage of muscle and abnormal subchondral bone reconstruction in rats with osteoarthritis(OA).Eighteen Sprague-Dawley rats were selected and randomly divided into three groups:the control group(CON group),the model group(OA group) and the oleanolic acid administration group(OLA group).The OA and OLA groups were established using anterior cruciate ligament dissection combined with partial meniscectomy(ACLT+PMMx) to establish a rat knee OA model,and the CON group underwent sham surgery.Rats in the OLA group were given 50 mg·(kg·d)^(-1) OLA by gavage daily,and rats in the CON and OA groups were given equal volumes of sterile saline containing 20 mL·L^(-1) Tween 80.After four consecutive weeks of dosing,knee,quadriceps and serum samples were taken.The rats were tested for joint pain using knee extension vocalization test and heat sensitivity test.Enzyme-linked immunosorbent assay to detect the levels of citrate synthase(CS),myosin heavy chain(MHC),interleukin 1(IL-1) and interleukin 6(IL-6) in rat muscle and the levels of osteocalcin(OCN) and C-terminal telopeptide of type I collagen(CTX-Ⅰ) in rat serum.Western blot was used to detect changes in Nrf2/NQO1/HO-1 pathway protein expression in muscle tissue.Micro-CT was used for subchondral bone scanning and quantitative analysis of bone tissue microstructure.The results showed that compared with the OA group,OLA could reduce the OA pain score(P<0.05),activate the muscle Nrf2/NQO1/HO-1 pathway,promote the expression of muscle CS and MHC,and down-regulate the levels of IL-1 and IL-6(P<0.05).In addition,percent bone volume(BV/TV),bone mineral density(BMD) and trabecular thickness(Tb.Th) were significantly increased(P<0.05) and expression of bone metabolic markers OCN and CTX-Ⅰ were significantly decreased(P<0.05) in subchondral bone of rats after OLA supplementation.The results suggest that OLA can inhibit the joint pain response in OA rats,inhibit muscle dysfunction in OA rats by regulating the
作者
马天文
吕良钰
于跃
贾丽娜
陈鸿
汤继浪
赵明超
王新宇
张建涛
高利
MA Tianwen;Lü Liangyu;YU Yue;JIA Lina;CHEN Hong;TANG Jilang;ZHAO Mingchao;WANG Xinyu;ZHANG Jiantao;GAO Li(College of Veterinary Medicine,Northeast Agricultural University,Heilongjiang Provincial Key Laboratory of Pathogenesis and Comparative Medicine of Animal Diseases,Harbin 150030,China)
出处
《畜牧兽医学报》
CAS
CSCD
北大核心
2022年第11期4081-4088,共8页
ACTA VETERINARIA ET ZOOTECHNICA SINICA
基金
国家重点研发计划资助项目(2017FYD0502200)
国家科技重大专项和重点研发项目省级资金资助项目(GX18B023)
黑龙江省应用技术研究与开发计划重大项目(GA18B203)。
关键词
骨关节炎
齐墩果酸
软骨下骨
肌肉
氧化应激
osteoarthritis
oleanolic acid
subchondral bone
muscle
oxidative stress
