摘要
目的:探讨大黄素联合碳酸氢钠通过抑制micro RNA-21(miR-21)降低糖尿病肾病尿蛋白水平的作用及机制。方法:构建DN小鼠,将小鼠分为对照组,大黄素组、碳酸氢钠组和联合用药组。实验组将大黄素及碳酸氢钠分别注射入糖尿病肾病小鼠体内,观察小鼠蛋白尿变化情况,并观察肾组织病理变化及相关指标包括miR-21、TGF-β、Smad-1、Col-Ⅳ变化情况。体外将足细胞分为对照组,大黄素组、碳酸氢钠组和联合用药组。实验组高糖环境下将大黄素及碳酸氢钠分别刺激足细胞,观察足细胞迁移能力变化情况,同时检测miR-21、TGF-β、Smad-1、Col-Ⅳ变化情况。改变miR-21水平,进一步观察大黄素及碳酸氢钠对足细胞及相关指标的影响。结果:糖尿病肾病小鼠对照组蛋白尿较实验组明显增加,联合用药组蛋白尿降低最明显(P<0.05)。联合用药组小鼠肾组织纤维化明显减轻。联合用药组肾组织miR-21、TGF-β、p-Smad-1、Col-IV水平降低明显(P<0.05)。体外实验中,联合用药组足细胞迁移能力较对照组明显恢复(P<0.05)。联合用药组miR-21、TGF-β、p-Smad-1、Col-IV水平亦明显较低(P<0.05)。改变miR-21水平后亦得到相应的结果。结论:大黄素联合碳酸氢钠能明显降低糖尿病肾病小鼠蛋白尿水平,两者具有协同作用。这一作用与调控miR-21、TGF-β水平密切相关。
Objective:To investigate the effect and mechanism of emodin combined with sodium bicarbonate on reducing urinary protein level in diabetic nephropathy through micro RNA-21(miR-21). Methods:Diabetic nephropathy mice were constructed and divided into control group, emodin group, sodium bicarbonate group and combination group. The level of proteinuria in mice were observed, and the pathological changes of renal tissues and related indexes including miR-21, TGF-β, Smad-1 and Collagen IV were observed. Podocyte cells were divided into control group, emodin group, combination group. The changes of podocyte migration ability were observed. Meanwhile, changes of Mir-21, TGF-β, Smad-1 and Col-IV were detected by RT-PCR and Western-blot. Results:The proteinuria of the diabetic nephropathy mice was significantly higher than that of the experimental group, and the proteinuria of combination group was the lowest(P<0.05). The combination group reduced the renal fibrosis significantly. combination group had renal tissue miR-21 and TGF-β、 The levels of p-smad-1 and Col-Ⅳ decreased significantly(P<0.05). In vitro, the podocyte migration ability of combination group was significantly restored compared with that of the control group(P<0.05). The levels of miR-21, TGF-β, p-Smad-1 and Col-IV were also significantly lower(P<0.05). Conclusion:Emodin combined with sodium bicarbonate can significantly reduce the proteinuria level in diabetic nephropathy mice, both have synergistic effect. This effect is closely related to the regulation of miR-21 and TGF-β.
作者
乔青燕
戴宾宾
战晓丽
翁梦洁
林贝多
潘阳彬
QIAO Qingyan;DAI Binbin;ZHAN Xiaoli(Department of Nephrology,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399)
出处
《中国中西医结合肾病杂志》
2022年第11期957-962,I0002,共7页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
上海市卫生健康委员会中医药科研项目基金资助项目(No.2020JP007)
复旦大学附属浦东医院院级基金资助项目(No.YJRCJJ201903,ZDZK2020-13)
复旦大学附属浦东医院院级人才项目(No.PY202002)。
关键词
大黄素
碳酸氢钠
糖尿病肾病
足细胞
损伤
Emodin
Sodium bicarbonate
Diabetic nephropathy
Podocyte injury
