Mice with focal segmental glomerular sclerosis are induced by adriamycin and its mechanism
10.3760/cma.j.issn.1001-7097.2016.08.010
- VernacularTitle:阿霉素诱导小鼠局灶性节段性肾小球硬化及其相关机制
- Author:
Yaqin KANG
;
Caili WANG
;
Yan MI
;
Dandan ZHOU
- Publication Type:Journal Article
- Keywords:
Glomerulosclerosis,focal segmental;
Oxidative stress;
Apoptosis;
MAP kinase signaling system
- From:
Chinese Journal of Nephrology
2016;32(8):617-622
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish adriamycin-induced focal segmental glomerular sclerosis(FSGS) mice model,and observe the expressions of and relation between oxidative stress and p38 MAPK signal pathway in renal injury.Methods Eight-week-old male Balb/c mice were randomly divided into FSGS group (n=20) and control group (n=20).In FSGS group mice were intravenously injected with a single dose of adriamycin (0.01 rag/g),and mice in control group were received saline with the same dose.At day 3,7,14,22 and 32,urine protein-to-urine creatinine ratio (P/C) was detected.At day 22 and 32,serum creatinine,blood urea nitrogen,nitric oxide (NO) and reactive oxygen species (ROS) in blood and urine,and ROS in kidney tissues were detected;changes of pathological morphology in renal tissue were analyzed by HE stain;the expressions of NF-κB,CD36,IL-13,BAX and Bcl-2 mRNA were detected by real time quantitative PCR;the expressions of NF-κB,p-p38 and p-ERK1/2 protein were detected by Western blotting.Results Compared with that in control group,P/C was gradually increasing in FSGS group,and peaked at day 22 (P ＜ 0.05).At day 22 and 32,mice had higher creatinine,serum creatinine,urea nitrogen,ROS and NO in FSGS group than those in control group (all P ＜ 0.05).There were mild hyperplasia of mesangial cells and mesangial matrix,segment with moderate exacerbations,podocytes with significant proliferation,and the capillary loops of the stenosed in the glomerular in FSGS group at day 32.Compared with those in control group,the mRNA expression of NF-κB,BAX,IL-13 and CD36,and the protein expressions of NF-κB and p-p38 MAPK were gradually increased in FSGS group,all showed statistical differences at day 32 (all P＜ 0.05);the expression of p-ERK1/2 was increased at day 22 (P ＜ 0.05) but was reduced at day 32 (P ＜ 0.05).Conclusions Adriamycin has induced FSGS in mice successfully,which may through oxidative stress activating p38,up-regulating NF-κB,increasing the inflammatory cytokines and inducing apoptosis pathways.
