IL-1β和IGF-1在幼兔发育性髋脱位髋臼软骨细胞中的表达和作用
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摘要
目的探讨白细胞介素-1β(IL-1β)和胰岛素样生长因子-1(IGF-1)在发育性髋脱位(DDH)髋臼软骨细胞增殖和凋亡中的作用及意义。方法选取4周龄实验幼兔32只,采用左侧后肢伸膝屈髋位管型石膏固定方法制作DDH动物模型,右侧后肢不做特殊处理作为对照侧,将幼兔平均分为4组(A、B、C、D组),分别在石膏固定8、12、16、20周后处死,采用免疫组织化学法和Western blot法检测双侧髋臼外缘软骨块及细胞中IL-1β和IGF-1的表达情况和蛋白水平,结果进行统计学分析。结果 IL-1β和IGF-1在双侧髋臼软骨细胞中均有不同程度的阳性表达;D组实验侧髋臼软骨中IL-1β的阳性率和蛋白水平最高,B、C、D组实验侧和对照侧比较,差异有统计学意义(P<0.05)。C组实验侧髋臼软骨中IGF-1的阳性率最高,B组实验侧髋臼软骨中IGF-1的蛋白水平最高,B、C组实验侧和对照侧比较,差异有统计学意义(P<0.05)。结论 IL-1β与IGF-1在DDH髋臼软骨细胞中的表达异常,导致软骨细胞增殖和凋亡之间失衡,可能是DDH发生髋关节退行性变的原因之一。
Objective To explore the role and significance of interleukin-1 beta(IL-1β)and insulin-like growth factor-1(IGF-1)in the proliferation and apoptosis of acetabular chondrocytes of developmental dislocation of the hip(DDH).Methods Thirty-two experimental rabbits aged 4 weeks old were selected,and the DDH animal model was made by plaster fixation in the knee extension and hip flexion position of the left hind limb.The right hind limb was not treated as a control side,and the rabbits were divided into four groups(group A,B,C and D)were sacrificed after 8,12,16 and 20 weeks of gypsum fixation.Immunohistochemistry and Western blot were used to detect IL-1βand IGF-1 in bilateral acetabular rim cartilage blocks.The expression and protein levels were analyzed and the results were statistically analyzed.Results IL-1βand IGF-1 were positively expressed in bilateral acetabular chondrocytes.The positive rate and protein content of IL-1βin experimental acetabular chondrocytes in group D were the highest.Compared with the control side,the difference among group B,C and D was statistically significant(P<0.05).The positive rate of IGF-1 in experimental acetabular cartilage in group C was the highest,while the protein content of that was the highest in group B.Compared with the control side,the difference between B and C was statistically significant(P<0.05).Conclusion The abnormal expression of IL-1βand IGF-1 leads to the imbalance between proliferation and apoptosis of acetabular chondrocytes in DDH,which may be one of the causes of hip degeneration resulted by DDH.
Objective To explore the role and significance of interleukin-1 beta(IL-1β)and insulin-like growth factor-1(IGF-1)in the proliferation and apoptosis of acetabular chondrocytes of developmental dislocation of the hip(DDH).Methods Thirty-two experimental rabbits aged 4 weeks old were selected,and the DDH animal model was made by plaster fixation in the knee extension and hip flexion position of the left hind limb.The right hind limb was not treated as a control side,and the rabbits were divided into four groups(group A,B,C and D)were sacrificed after 8,12,16 and 20 weeks of gypsum fixation.Immunohistochemistry and Western blot were used to detect IL-1βand IGF-1 in bilateral acetabular rim cartilage blocks.The expression and protein levels were analyzed and the results were statistically analyzed.Results IL-1βand IGF-1 were positively expressed in bilateral acetabular chondrocytes.The positive rate and protein content of IL-1βin experimental acetabular chondrocytes in group D were the highest.Compared with the control side,the difference among group B,C and D was statistically significant(P<0.05).The positive rate of IGF-1 in experimental acetabular cartilage in group C was the highest,while the protein content of that was the highest in group B.Compared with the control side,the difference between B and C was statistically significant(P<0.05).Conclusion The abnormal expression of IL-1βand IGF-1 leads to the imbalance between proliferation and apoptosis of acetabular chondrocytes in DDH,which may be one of the causes of hip degeneration resulted by DDH.
引文
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[15]PETERSE E F,CLEVEN A H,DE J Y,et al.No preclinical rationale for IGF1Rdirected therapy in chondrosarcoma of bone[J].BMC Cancer,2016,16:475.
[2]WEI Y S,LI D H,LIU W L,et al.Altered chondrocyte apoptosis status in developmental hip dysplasia in rabbits[J].Balkan Med J,2016,33(6):639-644.
[3]张保龙,邵增务.胰岛素样生长因子1和白介素1受体拮抗剂在骨性关节炎中的作用及研究进展[J].实用医学杂志,2009,25(8):1335-1337.
[4]SCHMIDT T A,GASTELUM N S,HAN E H,et al.Differential regulation of proteoglycan 4metabolism in cartilage by IL-1alpha,IGF-I,and TGF-beta1[J].Osteoarthritis?Cartilage,2008,16(1):90-97.
[5]王炳海,韦宜山,丁良甲,等.发育性髋关节脱位早期髋臼软骨细胞凋亡的实验研究[J].中国矫形外科杂志,2013,21(17):1755-1760.
[6]苏晓恩,孔志强,朱娟,等.膝关节骨关节炎软骨中YKL-40、IL-1β的表达及相关性探讨[J].重庆医学,2017,46(4):480-482.
[7]ELSAID K A,UBHE A,SHAMAN Z,et al.Intra-articular interleukin-1 receptor antagonist(IL1-ra)microspheres for posttraumatic osteoarthritis:in vitro biological activity and in vivo disease modifying effect[J].J Exp Orthop,2016,3(1):18.
[8]NASI S,EA H K,SO A,et al.Revisiting the role of interleukin-1pathway in osteoarthritis:interleukin-1αand-1β,and NLRP3inflammasome are not involved in the pathological features of the murine menisectomy model of osteoarthritis[J].Front Pharmacol,2017,8:282.
[9]熊寿良,徐宏光,王强,等.白细胞介素1β诱导软骨细胞中雷帕霉素靶蛋白信号通路[J].中华医学杂志,2017,97(7):540-544.
[10]BWALYA E C,KIM S,FANG J,et al.Pentosan polysulfate inhibits IL-1β-induced iNOS,c-Jun and HIF-1αupregulation in canine articular chondrocytes[J].PLoSOne,2017,12(5):e0177144.
[11]尹万乐,马利阁,尤笑迎,等.膝骨性关节炎患者关节滑液白细胞介素-1β和肿瘤坏死因子-α的表达及意义[J].中华实验外科杂志,2017,34(9):1593-1595.
[12]李宁,刘鸣,刘宏建,等.节律基因BMAL1调控人软骨细胞胰岛素样生长因子1信号传导[J].中华实验外科杂志,2018,35(2):292-296.
[13]WEI F Y,LEE J K,WEI L,et al.Correlation of insulinlike growth factor 1and osteoarthritic cartilage degradation:a spontaneous osteoarthritis in guinea-pig[J].Eur Rev Med Pharmacol Sci,2017,21(20):4493-4500.
[14]彭程,肖涛,罗远明,等.IGF-1对IL-1诱导的兔关节软骨细胞NO和PGE2影响[J].中南大学学报(医学版),2008,33(3):197-203.
[15]PETERSE E F,CLEVEN A H,DE J Y,et al.No preclinical rationale for IGF1Rdirected therapy in chondrosarcoma of bone[J].BMC Cancer,2016,16:475.