中医学报2023，Vol.38Issue(12)：2534-2541,8.DOI:10.16368/j.issn.1674-8999.2023.12.406
虫草素对大鼠肾缺血再灌注损伤铁死亡的影响
Effects of Cordycepin on Ferroptosis Induced by Renal Ischemia-Reperfusion Injury in Rats
摘要
Abstract
Objective:To investigate the effect of cordycepin on renal ischemia-reperfusion injury(RIRI)in rats based on ferroptosis.Method:24 rats were randomly divided into a control group,a model group,a cordycepin group(8 mg·kg-1),and an iron death inhib-itor group(5 mg·kg-1),with6 rats in each group.Rats in each group were given corresponding drugs intraperitoneally for7 days.Ex-cept for the control group,all other three groups of rats were used to construct RIRI models.PAS method was used to observe the patho-logical damage of rats'kidneys;Automatic biochemical analyzer was used to detect blood urea nitrogen(BUN)and serum creatinine(Scr)levels;Fe2+content in renal tissue supernatant was detected by using an iron analysis kit;Mitosox fluorescent probes was used to detect mitochondrial superoxide levels in renal tubular epithelial cells;Microporous plate reader was used to detect mitochondrial super-oxide levels;Flow cytometry was used to detect the apoptosis rate of rats in each group;Flow cytometry was used to detect ROS levels in rat kidney tissue and apoptosis of renal tubular epithelial cells;Western Blot was used to detect glutathione peroxidase 4(GPX4),mem-ber 11 of the solute carrier family 7(SLC7A11),ferritin heavy chain 1(FTH1),long chain acyl CoAsynthase 4(ACSL4),nuclear fac-tor E2 related factor 2(Nrf2),the expression levels of nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1)and cyclooxyge-nase-2(COX2)proteins.Results:Compared with the control group,the model group showed a significant increase in PAS positive staining area(P<0.01),Fe2+,BUN,Scr,ROS,mitochondrial superoxide levels,and cell apoptosis rate(P<0.05).The expression levels of GPX4,SLC7A11,FTH1,and Keap1 proteins were significantly downregulated(P<0.05),while the expression levels of AC-SL4,Nrf2,NOX1,and COX2 proteins were significantly upregulated(P<0.05);Compared with the model group,the area of PAS posi-tive staining in renal tissue of the cordycepin group and I/R + Ferrostatin-1 group was significantly reduced(P<0.01),while the levels of Fe2+,BUN,Scr,ROS,mitochondrial superoxide,and cell apoptosis rate were significantly reduced(P<0.05).The expression levels of GPX4,SLC7A11,FTH1,and Keap1 proteins were significantly up-regulated(P<0.05),while the expression levels of AC-SL4,Nrf2,NOX1,and COX2 proteins were significantly down-regulated(P<0.05).The PAS staining results showed that the expan-sion of the renal capsule and tubular lumen in the cordycepin group and ferroptosis inhibitor group rats was significantly reduced,the glomerular volume was relatively normal,the gap increased and interstitial edema improved significantly,and the integrity of the base-ment membrane was better.Conclusion:Cordycepin can improve renal ischemia-reperfusion injury in rats by inhibiting ferroptosis,and play a protective role in renal function.关键词
铁死亡/虫草素/肾缺血再灌注损伤/大鼠Key words
ferroptosis/cordycepin/renal ischemia-reperfusion injury/rat分类
医药卫生引用本文复制引用
罗进辉,童运涛,张慧,范倩倩,吕彬..虫草素对大鼠肾缺血再灌注损伤铁死亡的影响[J].中医学报,2023,38(12):2534-2541,8.基金项目
武汉市医学科研项目(WZ20Q07) （WZ20Q07）
