白肉灵芝调节Keap1/Nrf2/HO-1信号通路改善肾纤维化研究
Study on the Ameliorating Effect of Ganoderma leucocontextum on Renal Fibrosis via Keap1/Nrf2/HO-1 Signaling Pathway
张洛宁 1钱蕊 1王侨蓝 1韩天韵 1谢林伸1
作者信息
- 1. 四川大学华西公共卫生学院/四川大学华西第四医院,四川 成都 610041
- 折叠
摘要
目的 利用小鼠单侧输尿管结扎(UUO)模型探究白肉灵芝对肾纤维化的改善作用及潜在分子机制.方法 C57BL/6J小鼠予UUO手术建立肾脏纤维化模型,400、800mg/kg白肉灵芝水提物GLW给药7 d后取材,观察肾脏形态改变,检测小鼠血清肌酐、尿素氮等肾功能指标;病理采用HE和Masson染色观察肾脏结构改变及胶原沉积情况;免疫组化检测Keap1和Nrf2蛋白的表达情况;Western Blotting、qPCR检测各组α-SMA、Vimentin、MMP2、COL I、HO-1、Keap1、Nrf2的表达.结果 模型组小鼠肾脏肿胀明显,有大量尿液储留,血清Scr和BUN显著升高;病理显示肾实质萎缩、肾盂高度扩张、细胞肿胀、变性坏死,胶原沉积明显增多;α-SMA、Vimentin、MMP2、COL I、Keap1蛋白表达和mRNA水平明显增加,HO-1、Nrf2蛋白表达和mRNA水平显著降低,GLW干预后上述变化被显著逆转.结论 白肉灵芝可通过Keap1/Nrf2/HO-1信号通路显著改善UUO所致肾损伤和肾纤维化,为CKD的治疗提供一条潜在的新途径.
Abstract
Objective To explore the ameliorating effect of Ganoderma leucocontextum on renal fibrosis and its potential molecular mechanism by using the mouse unilateral ureteral ligation model.Methods C57BL/6J mice were operated on by UUO to establish renal fibrosis model.After 7 d of administration of 400 and 800 mg/kgGLW,kidney morphological changes were observed and renal function indexes such as serum creatinine and urea nitrogen were detected.The changes of renal structure and collagen deposition were observed by HE and Masson staining.The expressions of Keap1 and Nrf2 proteins were detected by immunohistochemistry.Western Blotting and qPCR were used to detect the expressions of α-SMA,Vimentin,MMP2,COL I,HO-1,Keap1 and Nrf2 in each group.Results In the model group,the kidney swelling was obvious,a large amount of urine was stored,and serum Scr and BUN were significantly increased.Pathology showed atrophy of renal parenchyma,high dilatation of renal pelvis,cell swelling,degeneration and necrosis,and increased collagen deposition.The protein expression and mRNA levels of α-SMA,Vimentin,MMP2,COL I and Keap 1 were significantly increased,while the protein expression and mRNA levels of HO-1 and Nrf2 were significantly decreased.The above changes were significantly reversed after GLW intervention.Conclusion GLW can significantly improve UUO-induced kidney injury and renal fibrosis through Keap1/Nrf2/HO-1 signaling pathway,providing a potential new approach for the treatment of CKD.
关键词
白肉灵芝/慢性肾脏病/肾纤维化/UUO/Keap1/Nrf2/HO-1Key words
G.leucocontextum/CKD/renal fibrosis/UUO/Keap1/Nrf2/HO-1引用本文复制引用
出版年
2024
NETL
NSTL
万方数据