Investigation on Mechanism of Jianzhong Bushen Xiaozheng Decoction Against Renal Interstitial Fibrosis in Regulating Wnt/β-catenin Signaling Pathway by MiRNA-139 / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the mechanism of Jianzhong Bushen Xiaozheng decoction in regulating the effect of miRNA139 on Wnt/<italic>β</italic>-catenin signaling pathway for renal interstitial fibrosis. Method:The 120 mice were randomly divided into sham operation group， unilateral ureteral obstruction （UUO） group， Jianzhong Bushen Xiaozheng decoction low， middle， high dose group， and Niaoduqing group. The UUO animal model was established to observe the morphological changes in mice. Intragastic administration was started from day 3 after modeling. The sham operation group and UUO group received the same amount of distilled water every day. The low， medium and high-dose groups received Jianzhong Bushen Xiaozheng decoction solution at 6，12，24 g·kg^-1·d^-1 respectively. The Niaoduqing group received 6.2 g·kg^-1·d^-1 Niaoduqing granule solution. After 14 d and 21 d， 28 d ， the morphological changes， general signs and renal interstitial fibrosis index of the obstructed side were observed， hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes of renal tissue. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） method was used to detect the miRNA-139 expression in renal tissue volume， Western blot was used to detect expression of beta serial proteins （<italic>β</italic>-catenin） and fibrinolytic enzyme activators inhibitor-1 （PAI-1） in renal tissues， and immunohistochemical assay was used for detection of matrix metalloproteinases-7 （MMP-7） protein expression at the obstruction side. Result:After 14， 21 and 28 days， the expression levels of <italic>β</italic>-catenin and PAI-1 in UUO group were higher than those in sham operation group（<italic>P</italic><0.05），while the expression levels of miRNA139 and MMP-7 protein were lower than those of sham operation group （<italic>P</italic><0.05）. The expression levels of <italic>β</italic>-catenin and PAI-1 proteins in mice after treatment in Niaoduqing group and the traditional Chinese medicine groups were lower than those in the UUO group（<italic>P</italic><0.05）， the expression of miRNA139 and MMP-7 proteins increased（<italic>P</italic><0.05）， and the efficacy of high-dose Jianzhong Bushen Xiaozheng decoction group was better than that of other dosage groups or Niaoduqing group（<italic>P</italic><0.05）. Conclusion:Jianzhong Bushen Xiaozheng decoction may regulate miRNA139 to mediate the process of renal interstitial fibrosis through the Wnt/ <italic>β</italic>-catenin pathway and delay the development of renal interstitial fibrosis to improve renal function.