中南医学科学杂志2023，Vol.51Issue(6)：834-838,5.DOI:10.15972/j.cnki.43-1509/r.2023.06.008
TRPV4抑制剂HC067047对小鼠膝骨关节炎软骨组织的影响
Effect of TRPV4 inhibitor HC067047 on cartilage tissue of knee osteoarthritis
摘要
Abstract
Aim To explore the effect of transient receptor potential vanilloid receptor 4(TRPV4)inhibitor HC067047 on osteoarthritis in Mice.Methods 30 mice were randomly divided into the sham group,the model group and HC067047 group.The sham group was only given an incision on the inner skin of the right knee joint patellar liga-ment without any treatment to the intra-articular structures.In contrast,the model group and the HC067047 group had their anterior cruciate ligaments and medial menisci anterior horns surgically removed to establish a knee osteoarthritis mod-el.They were then administered either physiological saline or HC067047 at a daily dose of 10 mg/kg by oral gavage.qRT-PCR was used to measure the mRNA expression level of TRPV4 in the mice cartilage tissue from each group.Safra-nin solid green staining was employed to assess the extent of joint cartilage damage,while HE staining was used to analyze changes in subchondral bone mass in the knee joint.Western blotting was used to detect the protein levels of cell pyropto-sis marker protein TRPV4,Caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apop-tosis-associated speck-like protein(ASC),and GSDMD-N in the cartilage tissue of each group.ELISA and Western blot-ting were utilized to measure the levels of inflammatory factors in serum and cartilage tissue.Results Compared to the Sham group,the model group exhibited a significant increase in levels of TRPV4,NLRP3,ASC,Caspase-1,GSDMD-N,interleukin(IL)-1β,and IL-18(P<0.05).In comparison to the model group,the HC067047 group showed significant reductions in levels of NLRP3,ASC,Caspase-1,GSDMD-N,IL-1β,and IL-18(P<0.05).HC067047 group showed significantly improved joint cartilage morphology,reduced the extent of osteoarthritis damage,and maintained subchondral bone mass.Conclusion HC067047 can inhibit chondrocytes pyrolysis and ameliorate the articular cartilage degenera-tion in osteoarthritis mice.关键词
HC067047/TRPV4/膝骨关节炎/关节软骨/细胞焦亡Key words
HC067047/TRPV4/ostoarthritis/aticular cartilage/cell pyrolysis分类
临床医学引用本文复制引用
刘德龙,杨瞻宇,陈昕彤,王奕威,关蕊,盛斌..TRPV4抑制剂HC067047对小鼠膝骨关节炎软骨组织的影响[J].中南医学科学杂志,2023,51(6):834-838,5.基金项目
湖南省自然科学基金(2019JJ40163、2022JJ4022) （2019JJ40163、2022JJ4022）
湖南省卫健委科研计划项目(202204074186) （202204074186）
