To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, t...To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.展开更多
Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats wer...Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.展开更多
文摘To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.
基金supported by the College Science Technology Research Project of Hebei Province(Grant No:ZD20131002)
文摘Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.
