文章摘要
彭侃,鲁超,胡守业,等.颗粒蛋白前体衍生物 Atsttrin对骨关节炎的保护作用及对 CD+4T细胞的调节作用[J].安徽医药,2022,26(1):6-11.
颗粒蛋白前体衍生物 Atsttrin对骨关节炎的保护作用及对 CD+4T细胞的调节作用
Protective effect of progranulin derivative Atsttrin on osteoarthritis and its regulation onCD+4Tcells
  
DOI:10.3969/j.issn.1009-6469.2022.01.002
中文关键词: 骨关节炎  颗粒蛋白前体  Atsttrin  肿瘤坏死因子 α  软骨细胞  CD+ T细胞亚群  大鼠, Sprague-Dawley 4
英文关键词: Osteoarthritis  Progranulin  Atsttrin  Tumor necrosis factor alpha  Chondrocytes  CD4+ T cell subsets  Rats, sprague-dawley
基金项目:陕西省重点研发计划项目( 2019SF-201)
作者单位
彭侃 西安交通大学附属红会医院关节病医院骨坏死与关节重建病区陕西西安 710054 
鲁超 西安交通大学附属红会医院关节病医院骨坏死与关节重建病区陕西西安 710054 
胡守业 西安交通大学附属红会医院关节病医院骨坏死与关节重建病区陕西西安 710054 
井文森 西安交通大学附属红会医院关节病医院骨坏死与关节重建病区陕西西安 710054 
王波 西安交通大学附属红会医院关节病医院骨坏死与关节重建病区陕西西安 710054 
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中文摘要:
      目的揭示颗粒蛋白前体衍生物 Atsttrin对骨关节炎的保护作用及对 CD+4T细胞的调节作用。方法本研究起止时间为 2018年 10月至 2019年 12月, 60只 5周龄 SD雄性大鼠购自西安交通大学医学部实验动物中心。采用膝关节前交叉韧带横断法建立骨关节炎大鼠模型,通过关节内注射 15 μL Atsttrin(1 μg/μL)对模型大鼠进行治疗,每周注射 1次,连续注射 4周。通过番红 O固绿染色检测软骨损伤程度,采用 OARSI评分系统评价软骨退化情况。 ELISA法检测大鼠血清干扰素 -γ(IFN-γ)、细胞介素 -4(IL-4)、白细胞介素 -17(IL-17)和转化生长因子 -β(TGF-β)水平。流式细胞仪分析血清 Th1、Th2、Th17和 Treg细胞白比例。应用终浓度为 10 μg/L的肿瘤坏死因子 -α(TNF-α)诱导滑膜细胞和软骨细胞 48 h,并分别用终浓度为 10 μg/L、20 μg/L、 50 μg/L的 Atsttrin处理滑膜细胞和软骨细胞 48 h。通过 5-溴-2-脱氧尿苷( BrdU)细胞增殖测定试剂盒检测滑膜或软骨细胞的增殖。通过 RT-PCR和 Western blotting检测软骨细胞中解聚蛋白样金属蛋白酶 -4(ADAMTS-4)、基质金属蛋白酶 -13(MMP-13)、 IFN-γ、IL-4、IL-17和 TGF-β的信使核糖核酸( mRNA)和蛋白表达。结果与模型组相比, Atsttrin组大鼠的膝关节软骨破坏情况明显减轻( P<0.05)。与模型组相比, Atsttrin组大鼠国际骨关节炎研究学会( OARSI)评分显著降低[(2.56±0.21)比
英文摘要:
      Objective To reveal the protective mechanism of progranulin derivative Atsttrin on osteoarthritis and its regulatory effect on CD+4 T cells.Methods The study started and ended from May 2018 to July 2019. 60 5-week-old male SD rats were purchased fromthe Experimental Animal Center of the Medical Department of Xi'an Jiaotong University. An osteoarthritis rat model was established byusing the anterior cruciate ligament transection of the knee joint. Intra-articular injection of 15 μL Atsttrin (1 μg / μL) was administeredto model rats, once a week for 4 weeks. The degree of cartilage damage was detected by safranin O fast green staining, and the cartilagedegradation was evaluated by the OARSI scoring system. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) were measured by ELISA. Flow cytometry was used to analyze the ratio of serum Th1,Th2, Th17 and Treg cells. Synovial cells and chondrocytes were induced with tumor necrosis factor-α (TNF-α) at a final concentration of10 μg/L for 48 h, and synovial cells and chondrocytes were incubated with Atsttrin at a final concentration of 10, 20, 50 μg/L for 48 h.The 5-bromo-2-deoxyuridine (BrdU) cell proliferation assay kit was used to assess the proliferation of synovial or chondrocytes. The mes-senger ribonucleic acid (mRNA) and protein expressions of disaggregated protein-like metalloproteinase-4 (ADAMTS-4), matrix metallo-proteinase-13 (MMP-13), IFN-γ, IL-4, IL-17 and TGF-β in chondrocytes were detected by RT-PCR and Western blotting.Results Com-pared with the model group, the knee cartilage destruction in the Atsttrin group was greatly reduced (P<0.05). Compared with the model group (2.56±0.21), the International Osteoarthritis Research Society (OARSI) score of the Atsttrin group (1.08±0.11) was significantlylower (P=0.001). The serum levels of IFN-γ and IL-17 in the Atsttrin group were lower than those in the model group , while the IL-4 and TGF-β were higher (P<0.05). Compared with the model group, the ratio of serum Th1 and Th17 cells in Atsttrin group decreased rapidly,while the ratio of Th2 and Treg cells increased dramatically (P<0.05). Atsttrin administration vastly reduced the proliferation of synovial cells induced by TNF-α and increased the proliferation of chondrocytes induced by TNF-α(P<0.05). Atsttrin tremendously down-regulat-ed the mRNA and protein expression levels of ADAMTS-4, MMP-13, IFN-γ, and IL-17 in chondrocytes induced by TNF-α and up-regu-lated the expression levels of IL-4 and TGF-β(P<0.05).Conclusion Atsttrin can maintain the stability of the microenvironment in thejoint by inhibiting synovial cell proliferation, promoting chondrocyte proliferation, and inhibiting cartilage mechanism degradation. In ad-dition, Atsttrin's articular cartilage protection is related to correcting the imbalance of Th1/Th2 cells and Th17/Treg cells.
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