黄芩素通过促进miR-29a-3p抑制MAP2K6改善骨性关节炎模型大鼠软骨细胞退化

Mechanism of Baicalein on Improving Cartilage Degeneration in OA Model Rats by Promoting miR-29a-3p to Inhibit on MAP2K6

目的:探索黄芩素(Baicalein)改善软骨细胞退化的可能机制。方法:用不同浓度黄芩素处理OA大鼠,观察软骨退化情况,并检测炎性细胞因子水平。用不同剂量黄芩素处理OA细胞模型,检测各组细胞的活力及凋亡情况,双荧光素酶报告验证miR-29a-3p、MAP2K6的靶向关系。结果:与假手术组比较,OA模型组大鼠血清中IL-1β、IL-6、TNF-α水平显著增高,细胞活力显著降低,细胞凋亡率显著增高,与模型对照组比较,黄芩素10、20、30 mg/kg能够显著降低OA模型血清中IL-1β、IL-6、TNF-α水平,能够显著改善OA大鼠软骨细胞活性抑制及凋亡情况,能够缓解OA模型软骨组织番红氧失染情况;miR-29a-3p与MAP2K6存在靶向关系,黄芩素10μmol/L能够明显下调OA细胞中MAP2K6、p38/p-p38、MAX蛋白表达水平。结论:黄芩素可以通过调节miR-29a-3p靶向抑制MAP2K6的磷酸化,提高软骨细胞活性,抑制细胞凋亡从而改善OA引起的软骨细胞退化。

Objective:To explore the possible mechanism of Baicalein on improving chondrocytes degeneration.Methods:The osteoarthritis(OA)rats was treated with different concentrations of Baicalein.The cartilage degradation was observed.The inflammatory cytokine levels were detected.OA cell models were treated with different doses of Baicalein.The cell viability and apoptosis in each group were detected.The dual luciferase assay was performed to verify targeting relationship between miR-29 a-3 p and MAP2 K6.Results:Compared with the sham operation group,serum levels of IL-1β,IL-6 and TNF-αin OA model group were significantly increased,the cell viability was decreased and the apoptosis was increased.Compared with the model group,serum levels of IL-1β,IL-6 and TNF-αin OA model group were significantly decreased in Baicalein groups(10,20,30 mg/kg),the inhibition of chondrocyte activity and the apoptosis were significantly improved,also the safranine oxygen staining loss of the cartilage tissue in OA model was alleviated.There was the targeting relationship between miR-29 a-3 p and MAP2 K6.10μmol/L Baicalein group reduced expression levels of MAP2 K6,p38/p-p38 and MAX protein in OA cells.Conclusion:Baicalein can improve the chondrocyte vitality and inhibit the apoptosis by regulating miR-29 a-3 p for targeted inhibition of MAP2 K6 phosphorylation,thus to improve chondrocytes degeneration caused by OA.