丹酚酸B减轻骨关节炎模型大鼠软骨组织损伤  

Salvianolic acid B alleviates cartilage tissue damage in rat models with osteoarthritis

作　　者：骞立刚[1] 孙博[1] 于泊[1] 陈康 马铮[1] 陈涛平[1] 王云飞[1] QIAN Ligang;SUN Bo;YU Bo;CHEN Kang;MA Zheng;CHEN Taoping;WANG Yunfei(Department of Orthopedics,the Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院骨科,河北保定071000

出　　处：《基础医学与临床》2023年第1期159-164,共6页Basic and Clinical Medicine

摘　　要：目的探究丹酚酸B对骨关节炎模型大鼠的软骨组织损伤、低氧诱导因子-1(HIF-1)和血管内皮生长因子(VEGF)的影响。方法构建骨关节炎模型大鼠,大鼠随机分为假手术组、骨关节炎组[切断交叉韧带法(ACLT)]、尼美舒利组、丹酚酸B高(40 mg/kg)和低(10 mg/kg)剂量组及丹酚酸B+HIF-1激活组,每组12只。显微CT机检测关节处骨结构;番红固绿染色和Masson染色观察软骨组织病理学变化;检测血清白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量、诱导性一氧化氮合酶(iNOS)的活性;Western blot检测软骨组织HIF-1、VEGF、基质金属蛋白酶13(MMP-13)及活化的半胱氨酸天冬氨酸蛋白酶3(ceaved caspase-3)表达。结果与假手术组相比,骨关节炎组软骨组织损伤严重,踝骨骨体积分数(BV/TV)降低,踝骨表面积与骨体积比值(BSA/BV)、血清中IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13及cleaved caspase-3蛋白表达升高(P<0.05);与骨关节炎组相比,尼美舒利组、丹酚酸B高和低剂量组软骨组织逐渐恢复,踝骨BV/TV升高,BSA/BV、血清IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13和cleaved caspase-3蛋白表达量降低(P<0.05);与丹酚酸B高剂量组相比,丹酚酸B+HIF-1激活组软骨组织损伤加重,踝骨BV/TV降低,BSA/BV、血清IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13及cleaved caspase-3蛋白表达升高(P<0.05)。结论丹酚酸B可通过调控HIF-1/VEGF通路,抑制HIF-1、VEGF表达,缓解骨关节炎。Objective To explore whether salvianolic acid B affects cartilage tissue damage,hypoxia-inducible factor-1(HIF-1)and vascular endothelial growth factor(VEGF)in osteoarthritis rats.Methods A rat model of osteoarthritis was constructed,and rats were randomly divided into sham operation group,osteoarthritis group(anterior cruciate ligment transection,ACLT),nimesulide group,salvianolic acid B high(40 mg/kg),and low(10 mg/kg)dose salvianolic acid B group,and salvianolic acid B+HIF-1 activation group,with 12 rats in each group.The bone structure at the joints of the rats in each group was measured and analyzed by micro-CT machine;The histopathological changes of cartilage were observed by safranin fast green staining and Masson staining;The contents of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and the activity of inducible nitric oxide syn-thase(iNOS)in rats were measured;The expression levels of HIF-1,VEGF,matrix metalloproteinase 13(MMP-13)and activated caspase-3(cleaved caspase-3)in rat cartilage tissue were measured by Western blot.Results Compared with the sham operation group,the cartilage tissue damage of the rats in the osteoarthritis group was severe,and the bone volume fraction(BV/TV)of the ankle bone was decreased,the ratio of ankle bone surface area to bone volume(BSA/BV),serum IL-6,TNF-αcontents,iNOS activity,cartilage HIF-1,VEGF,MMP-13,and cleaved caspase-3 protein expression were increased(P<0.05);Compared with the osteoarthritis group,the cartilage tissue of the nimesulide group,the salvianolic acid B high and low dose salvianolic acid B group gradually recovered,and the ankle BV/TV was increased,BSA/BV,serum IL-6,TNF-αcontents,iNOS activity,cartilage HIF-1,VEGF,MMP-13,and cleaved caspase-3 protein expression were decreased(P<0.05);Compared with the high-dose salvianolic acid B group,the salvianolic acid B+HIF-1 activation group had increased cartilage tissue injury,and ankle BV/TV was lower,BSA/BV,serum IL-6,TNF-αcontents,iNOS activity,cartilage HIF-1,VEGF,MMP-13,and cleaved caspase-3 prot

关 键 词：切断交叉韧带法 骨关节炎 丹酚酸B 低氧诱导因子-1 血管内皮生长因子 

分 类 号：R965[医药卫生—药理学]