基于Zinc-ZIP8-MTF1轴研究独活寄生汤治疗膝骨关节炎的作用机制

Study of the Mechanism of Du Huo Ji Sheng Decoction in The Treatment of Knee Osteoarthritis Based on the Zinc-ZIP8-MTF1 Axis

目的观察独活寄生汤调控Zinc-ZIP8-MTF1轴,探讨独活寄生汤治疗膝骨关节炎的作用机制。方法选用54只小鼠,分为独活寄生汤组(DHJST组)、对照组(Model组)、空白组(Control组),每组18只,Model组、DHJST组构建小鼠膝骨关节炎模型,DHJST组予独活寄生汤,另两组予生理盐水,观察小鼠膝关节软骨病理改变,检测软骨细胞内Zn^(2+)浓度及锌转运蛋白(ZIP8、ZNT9)、金属调节转录因子(MTF1)、基质金属蛋白酶-3(MMP3)、基质金属蛋白酶-13(MMP13)表达。结果与Model组比较,DHJST组小鼠软骨组织病理学评分明显下降,软骨细胞内Zn^(2+)含量大幅减少,软骨组织中ZIP8、ZNT9、MTF1、MMP3、MMP13 mRNA表达降低(P<0.05)。结论Zinc-ZIP8-MTF1轴在独活寄生汤治疗KOA的机制中发挥了一定作用,但独活寄生汤对Zn2+进出软骨细胞的关键环节没有明显影响。

Objective To observe the regulation of the Zinc-ZIP8-MTF1 axis by Duhuoji Decoction and to investigate the mechanism of Duhuojii Decoction in the treatment of knee osteoarthritis.Methods 54 mice were selected and divided into Duhuo Jisitang group(DHJST group),control group(Model group),and blank group(Control group),with 18 mice in each group.Mouse knee osteoarthritis models were constructed in Model group and DHJST group..The DHJST group was given Duhuojii Decoction by gavage,and the other two groups were given normal saline by gavage.Intact knee joints were taken to observe the pathological changes of mouse knee cartilage,and to detect the concentration of Zn^(2+) in chondrocytes and the expression of zinc transporter(ZIP8,ZNT9),metal regulatory transcription factor(MTF1),matrix metalloproteinase-3(MMP3),and matrix metalloproteinase-13(MMP13).Results Compared with the Model group,the histopathological score of cartilage in the DHJST group was significantly decreased,the level of Zn^(2+) in chondrocytes was greatly reduced,and the expression of ZIP8,ZNT9,MTF1,MMP3,and MMP13 mRNA in cartilage tissues was significantly decreased(P<0.05).Conclusion Zinc-ZIP8-MTF1 axis played a role in the treatment of KOA by Duhuojijietang,but Duhuojijietang has no significant effects on the key processes in the transportation of Zn2+in and out of chondrocytes.