Rosiglitazone Regulates PPARγ/NLRP3 Mediated Pyroptosis Pathway Alleviates Acute Renal Injury Induced by Contrast-Induced Acute Kidney Injury in Rats
Objective To investigate the mechanism of rosiglitazone (RSG)in relieving contrast induced acute renal injury (CI-AKI)in rats. Methods Male SD rats were randomly divided into control group (Control),CI-AKI model group (Model),RSG treatment group [RSG,40 mg/(kg·d)],peroxi-some proliferator activated receptor γ(PPARγ)inhibitor group (T0070907,0.15 mg/mL),6 in each group. CI-AKI rat model was established and the serum and kidney tissues of rats in each group were collected 3 days after administration,and the indexes of renal function,the levels of serum creatinine (Scr)and blood urea nitrogen (BUN)were measured;Determination of interleukin-1β(IL-1β),IL-18, reactive oxygen species (ROS)and nitric oxide (NO)content by ELISA;Hematoxylin-eosin (H-E)stai-ning was used to observe the renal histopathological changes;Immunohistochemical (IHC)staining exami-nation PPARγ,NLRP3 protein expression;TUNEL staining was used to detect the pyroptosis index of renal tissue;Detection of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1 ),gasdermin D (GSDMD),IL-1β and IL-18 protein expression in renal tissue by Western-blot. Results Compared with control group,the contents of Scr, BUN,IL-1β,IL-18,ROS and NO were significantly increased (P<0.05 or P<0.01 ),renal tissue showed obvious pathological damage,the index of pyroptosis,the protein expression of NLRP3,ASC, Caspase-1,GSDMD,IL-1β and IL-18 were increased (P<0.01 ),the protein expression PPARγ was decreased in model group (P<0.01). Compared with model group,the contents of erum Scr,BUN, IL-1β,IL-18,ROS and NO were significantly decreased (P<0.05 or P<0.01). Alleviation of patholog-ical damage of renal tissue,the index of pyroptosis,the protein expression of NLRP3,ASC,Caspase-1, GSDMD,IL-1β and IL-18 were decreased (P<0.01),the protein expression PPARγ was increased in RSG group (P<0.01). Compared with RSG group,T0070907 can reverse the above index changes of CI-AKI rats treated with RSG. Conclusion RSG can improve rat CI-AKI,and promote PPARγ expres-sion,inhibit the activation of NLRP3 inflammasome mediated pyroptosis.
万方数据
维普
