治疗型关节炎护膝对膝骨关节炎兔关节液中转化生长因子β及胰岛素样生长因子的影响

Effect of therapeutic knee-pads for arthritis on transforming growth factor-beta and insulin-like growth factors in joint fluid of rabbits with knee osteoarthritis

目的:观察治疗型关节炎护膝对膝骨关节炎兔关节液中转化生长因子-β及胰岛素样生长因子的影响,探讨治疗型关节炎护膝治疗膝骨关节炎的可能作用机制。方法:采用抽签法将54只日本大耳白兔随机分为6组,正常组10只,模型组9只,对照组9只,实验1组9只,实验2组8只,实验3组9只。用改良Hulth法对模型组、对照组、实验1组、实验2组及实验3组实验兔的右膝关节进行造模。造模后正常组及模型组常规喂养,不进行干预;对照组采用微波仪治疗;3个实验组均采用治疗型关节炎护膝治疗,其中实验1组选用疏密波模式,实验2组选用热疗模式,实验3组选用疏密波+热疗模式。造模后第16周分别拍摄各组实验兔双膝正位X线片,观察其膝关节的宏观结构,同时采用放射免疫分析法测定造模侧关节液中转化生长因子β和胰岛素样生长因子的含量。结果:①X线片表现。正常组膝关节内外侧间隙正常,关节表面光滑平整,边缘规则整齐,软骨下骨密度均匀;模型组膝关节内侧间隙明显变窄,关节表面变形,关节边缘可见明显骨赘,软骨下骨密度明显增高;对照组关节变化情况介于实验1组和实验3组之间;实验1组关节变化基本与模型组相同;实验2组关节变化情况介于实验1组和实验3组之间;实验3组膝关节内侧间隙变窄,关节面变形,关节边缘可见轻微骨赘形成,软骨下骨密度增高。②转化生长因子β含量。各组间转化生长因子β含量比较,差异有统计学意义(F=23.757,P=0.000)。组间两两比较,正常组低于模型组、对照组、实验1组、实验2组及实验3组(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000);模型组低于对照组、实验2组及实验3组(P=0.000,P=0.000,P=0.000);实验1组低于对照组、实验2组及实验3组(P=0.028,P=0.007,P=0.002);其余各组间比较,差异均无统计学意义。③胰岛素样生长因子含量。各组间胰岛素样生长因子含量比较,差异有统计学意义(F=9.074,P=0.000)。组间两两比较,正常组低于模型组、对照组、实验1组、实验2组及实验3组(P=0.040,P=0.000,P=0.027,P=0.000,P=0.000);模型组低于对照组、实验2组及实验3组(P=0.012,P=0.004,P=0.000);实验1组低于对照组、实验2组及实验3组(P=0.026、P=0.010、P=0.001);其余各组间比较,差异均无统计学意义。结论:治疗型关节炎护膝治疗膝骨关节炎的机制可能是提高关节滑膜和关节软骨中转化生长因子β及胰岛素样生长因子的表达水平,促进软骨细胞增殖分化及细胞外基质合成,同时抑制滑膜炎症反应,从而起到延缓关节软骨退变、促进关节软骨修复的作用。

Objective：To observe the effect of therapeutic knee-pads for arthritis on transforming growth factor-beta（TGF-β）and insulin-like growth factors（IGF）in joint fluid of rabbits with knee osteoarthritis（KOA）,and to explore the possible mechanism of therapeutic knee-pads for arthritis in the treatment of KOA.Methods：Fifty-four Japanese white rabbits were randomly divided into 6 groups,10 cases in normal group,9 cases in model group,9 cases in control group,9 cases in experimental group 1,8 cases in experimental group 2 and 9 cases in experimental group 3.The rabbits were operated on the right knee-joint to build models of knee osteoarthritis using the modified Hulth method in model group,control group,experimental group 1,experimental group 2 and experimental group 3.After modeling,rabbits in normal group and model group were administrated with conventional feeding without intervention;rabbits in control group were administrated with microwave apparatus treatment;rabbits in experimental group 1 were administrated with therapeutic knee-pads for arthritis in the-mode of density wave;rabbits in experimental group 2 were administrated with therapeutic knee-pads for arthritis in the mode of thermotherapy;rabbits in experimental group 3 were administrated with therapeutic knee-pads for arthritis in the mode of density wave and thermotherapy.The macrostructure of knee joints of the rabbits in the 6 groups were observed through the X-ray pictures of their both knees photographed in the anteroposterior position at the 16th week after modeling.Meanwhile,the contents of TGF-β and IGF in the fluid of modeling joints were measured through radioimmunoassay.Results：①X-ray picture：Such situations as normal medial and lateral knee joint gap,smooth joint surface,intact regular edges of joint and uniform subchondral bone were found in normal group.Obvious narrow medial knee joint gap,deformed surface of joint,phanic osteophyma on the edge of joint and obviously increased density of subchondral bone were found in model group.The changes of knee joint of patients in control group lay somewhere between those of experimental group 1 and experimental group 3.The changes of knee joint of patients in experimental group 1 were same as those of model group basically.The changes of knee joint of patients in experimental group 2 lay somewhere between those of experimental group 1 and experimental group 3.Narrow medial knee joint gap,deformed surface of joint,unconspicuous osteophyma on the edge of the joint and increased density of subchondral bone were found in experimental group 3.②TGF-beta content：There was statistical difference in TGF-beta contents among the 6 groups（F=23.757,P=0.000）.TGF-beta contents of normal group were lower than those of model group,control group,experimental group 1,experimental group 2 and experimental group 3 respectively（P=0.000,P=0.000,P=0.000,P=0.000,P=0.000）.TGF-beta contents of model group were lower than those of control group,experimental group 2 and experimental group 3 respectively（P=0.000,P=0.000,P=0.000）.TGF-beta contents of experimental group 1 were lower than those of control group,experimental group 2 and experimental group 3 respectively（P=0.028,P=0.007,P=0.002）.There was no statistical difference between any other couple groups.③IGF content：there was statistical difference in IGF contents among the 6 groups（F=9.074,P=0.000）.TGF-beta contents of normal group were lower than those of model group,control group,experimental group 1,experimental group 2 and experimental group 3 respectively（P=0.040,P=0.000,P=0.027,P=0.000,P=0.000）.TGF-beta contents of model group were lower than those of control group,experimental group 2 and experimental group 3 respectively（P=0.012,P=0.004,P=0.000）.TGF-beta contents of experimental group 1 were lower than those of control group,experimental group 2 and experimental group 3 respectively（P=0.026,P=0.010,P=0.001）.There was no statistical difference between any other couple groups.Conclusion：The mechanism of therapeutic knee-pads for arthritis in the treatment of KOA maybe rely on the raise of expression levels of TGF-β and IGF in articular synovium and articular cartilage,and on the promotion of cartilage cells proliferation and differentiation and synthesis of extracellular matrix as well on the restraination of inflammatory reaction in the synovium on the purpose of slowing down the regression of articular cartilage and improving its repair.