赣南医科大学学报2025,Vol.45Issue(12):1131-1137,7.DOI:10.3969/j.issn.2097-7174.2025.12.002
冬凌草甲素抗系膜增生性肾小球肾炎的作用及机制研究
Study on the effect and mechanism of oridonin on mesangial proliferative glomerulonephritis
摘要
Abstract
Objective:To explore the effects of oridonin(ORI)on the proliferation,cell cycle distribution,and apoptosis of rat glomerular mesangial cells,providing new ideas for drug intervention in mesangial proliferative glomerulonephritis(MsPGN).Methods:⑴ A rat mesangial cell proliferation model was constructed using 25%fetal bovine serum(FBS).The effects of ORI on the proliferation and apoptosis of rat mesangial cells were evaluated through MTT assay,cell cycle assay,apoptosis assay and laser confocal microscopy.⑵ A MsPGN mouse model was established using Freund's complete adjuvant and LPS.The effect of ORI on the proliferation of mesangial cells in kidney tissue was evaluated.Results:⑴ Compared with the model control group,the cell proliferation ability of the 5 µmol·L-1 ORI group,10 µmol·L-1 ORI group,15 µmol·L-1 ORI group,and 20 µmol·L-1 ORI group decreased,and the differences were statistically significant(P<0.05).Moreover,ORI inhibited the proliferation of mesangial cells in a concentration-dependent manner.The 24-hour half-maximal inhibitory concentration(IC50)of ORI was 12.88 µmol·L-1.The 15 µmol·L-1 ORI group and 20 µmol·L-1 ORI group significantly inhibited the proliferation of rat mesangial cells.⑵ The proportion of cells in the G0/G1 phase in the 15 µmol·L-1 ORI group(64.93±6.69)%was significantly different from that in the model control group(40.23±7.83)%(P<0.05);the proportions of cells in the S phase and G2/M phase were not statistically different from those in the model control group(P>0.05).⑶ The total apoptosis rates of the normal control group,model control group,and 15 µmol·L-1 ORI group were(6.63±6.90)%,(5.03±2.64)%,and(57.03±8.18)%,respectively.The early apoptosis rate,late apoptosis rate,and total apoptosis rate of the 15 µmol·L-1 ORI group were higher than those of the normal control group and model control group,and the differences were statistically significant(P<0.05),and cell apoptosis was mainly early apoptosis.⑷ Macroscopically,the surface of kidneys of the normal control group was smooth and light brown,while those in the model control group were significantly enlarged and congested,presenting dark brown.The color of kidneys of the low concentration group and high concentration group gradually became lighter,and their volumes also decreased.⑸ Immunohistochemical results showed that the number of Ki-67 positive cells in the kidneys of the model group was higher than that in the control group,and the number of Ki-67 positive cells in the kidneys of the high and low concentration groups was significantly reduced.⑹ HE staining:the cells in the mesangial area of the normal control group were sparse,while those in the model control group were increased.The number of cells in the mesangial area was reduced in the low concentration group and high concentration group.PAS staining:the thickness of the basement membrane in the normal control group was uniform and clear,while that in the model control group was thickened,and the degree of thickening of the basement membrane in the low concentration group and high concentration group was reduced.Trichrome staining:there was no obvious blue collagen fiber deposition in the renal glomeruli or around the renal glomeruli in the normal control group,while in the model control group,blue collagen fibers were significantly accumulated in the renal glomeruli or around them,and the deposition of blue collagen fibers in the renal glomeruli or around them was reduced in the low concentration group and high concentration group.Conclusion:Oridonin effectively inhibits the pathological proliferation of renal mesangial cells,induces their arrest in the G0/G1 phase,and promotes apoptosis,demonstrating broad potential as a promising therapeutic agent for mesangial proliferative glomerulonephritis.关键词
冬凌草甲素/系膜细胞/细胞周期阻滞/细胞凋亡/系膜增生性肾小球肾炎Key words
Oridonin/Mesangial cells/Cell cycle arrest/Apoptosis/Mesangial proliferative glomerulonephritis分类
医药卫生引用本文复制引用
郭艳,钟悦,李俊霖,刘金英,谢富华,王润秀..冬凌草甲素抗系膜增生性肾小球肾炎的作用及机制研究[J].赣南医科大学学报,2025,45(12):1131-1137,7.基金项目
江西省教育厅科学技术研究项目(GJJ201526) (GJJ201526)
江西省自然科学基金项目(20242BAB26171) (20242BAB26171)