Effect of Crocin on diabetic cardiomyopathy in rats via p38 MAPK/NF-κB signaling pathway
Objective It is to investigate the effect of Crocin on diabetic cardiomyopathy(DCM)in rats via p38 mito-gen-activated protein kinase/nuclear factor-κB(p38 MAPK/NF-κB)signaling pathway.Methods Forty-five Wistar rats were taken,in which 8 rats were randomly selected as normal group,and the remaining rats were fed with high-sugar and high-fat diet for 12 weeks and loaded with 30 mg/kg streptozotocin to establish models of DCM.32 successfully modeled rats were randomly divided into model group,Crocin group,Crocin+p38 MAPK inhibitor group and Crocin+p38 MAPK agonist group,with 8 rats in each group.The Crocin group was given 50 mg/kg Crocin intraperitoneally,the Crocin+p38 MAPK inhibitor group was given 50 mg/kg Crocin and 5 mg/kg SB203580 intraperitoneally,the Crocin+p38 MAPK ago-nist group was given 50 mg/kg Crocin and 2 mg/kg ANS intraperitoneally,and the normal group and model group were giv-en equal volumes of normal saline by intraperitoneal injection,all once daily.After 12 weeks of administration,the cardiac function indexes[left ventricular end-systolic diameter index(LVESD),left ventricular end diastolic diameter(LVEDD),left ventricular fractional shortening(LVFS)]of the rats were detected by cardiac ultrasound,the serum levels of myocar-dial enzyme[aspartate transaminase(AST),lactate dehydrogenase(LDH),creatine kinase isoenzyme MB(CK-MB)]and inflammatory factors[interleukin-1 β(IL-1 β),IL-18,tumor necrosis factor-α(TNF-α)]in myocardial tissue were detected by ELISA,the myocardial tissue pathological changes and fibrosis were observed by hematoxylin-eosin or masson staining,The mRNA and protein expressions of p38 MAPK,NF-κB p65,transforming growth faction-β1(TGF-β1),type Ⅰcollagen(Col-Ⅰ)were detected by RT-PCR or immunohistochemical(IHC)method.Results Compared with the model group,the LVESD,LVEDD,and serum levels of AST,LDH,CK-MB,IL-1 β,IL-18,TNF-α in the Crocin group and Crocin+p38 MAPK inhibitor group were significantly decreased,and the LVFS was significantly increased(all P＜0.05);the myocardial tissue pathological changes and fibrosis were significantly improved,the injury score and collagen volume fraction were significantly decreased(all P＜0.05);the mRNA and protein expressions of p38 MAPK,NF-κB p65,TGF-β,,Col-Ⅰ were significantly decreased(all P＜0.05).Compared with the Crocin group,SB203580 could significantly en-hance the regulatory effects of Crocin on cardiac function indexes and levels of myocardial enzyme and inflammatory factors,myocardial tissue pathological changes and fibrosis,p38 MAPK/NF-κB signaling pathway related mRNA and protein ex-pression in DCM rats;while ANS could reverse these effects of Crocin on DCM rats.Conclusion Crocin may alleviate in-flammation and tissue fibrosis via inhibiting the p38 MAPK/NF-κB signaling pathway,thereby protect DCM rats.
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