中国临床药理学杂志2024，Vol.40Issue(6)：879-883,5.DOI:10.13699/j.cnki.1001-6821.2024.06.020
雷公藤多苷调控鞘氨醇激酶信号通路改善IgA肾病大鼠肾损伤的作用研究
Study of action of multi-glycosides of Tripterygium wilfordii in regulating sphingosine kinases pathway to improve renal injury in IgA nephropathy rats
摘要
Abstract
Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9％NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P＜0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.关键词
雷公藤多苷片/免疫球蛋白A肾病/肾损伤/鞘氨醇激酶1/1-磷酸鞘氨醇受体2Key words
multi-glycosides of Tripterygium wilfordii/immunoglobulin A nephropathy/renal injury/sphingosine kinase 1/sphingosine 1-phosphate receptor 2分类
医药卫生引用本文复制引用
孟子璐,宋纯东,王耀献,张霞,丁樱,任献青,翟文生..雷公藤多苷调控鞘氨醇激酶信号通路改善IgA肾病大鼠肾损伤的作用研究[J].中国临床药理学杂志,2024,40(6):879-883,5.基金项目
国家自然科学基金资助项目(82074493) （82074493）
河南省卫健委国家中医临床研究基地科研专项基金资助项目(2022JDZX003) （2022JDZX003）
河南省中医药科学研究重大专项基金资助项目(2023ZYZD02) （2023ZYZD02）
河南省中医药学科领军人才基金资助项目(豫卫中医函[2021]8号) （豫卫中医函[2021]8号）
