Effects of pyrrolidine dithiocarbamate on nuclear factor-κB/interleukin-6 signaling pathway in rats with chronic mixed reflux esophagitis / 中华消化杂志

ABSTRACT

Objective To observe the protective effects of nuclear factor (NF) κB inhibitor pyrrolidine dithiocarbamate (PDTC) on chronic mixed reflux esophagitis in rats and its influence on NF-κB/interleukin (IL)-6 signaling pathway.Method A total of 40 healthy male Sprague-Dawley (SD) rats were divided into healthy control group,sham operation group,model control group,omeprazole group and PDTC group with eight rats in each group.Except rats in healthy control group and sham operation group,mixed reflux esophagitis model were established in all the other groups.The rats of healthy control group,sham operation group and model control group were all intraperitoneally injected with 2 mL 0.9％ NaCl,rats of omeprazole group were intraperitoneally injected with omeprazole 20 mg/kg,and rats of PDTC group were intraperitoneally injected with PDTC 100 mg/kg every day.After six weeks,the rats were sacrificed,the morphological changes of esophageal tissues were observed and scored by visual inspection and under light microscope.The serum levels of NF-κB p65 and IL-6 in rats of each group were assessed by enzyme linked immunoassay (ELISA).t test was performed for mean comparison among groups.Results The scores of esophageal mucosa judged by visual inspection of healthy control group,sham operation group,model control group,omeprazole group and PDTC group were 0.000 20.000,0.000±0.000,2.250± 0.707,1.125 ± 0.835 and 1.429± 0.535,respectively.The pathological scores were 0.00020.000,0.000±0.000,2.625±0.518,1.500±0.535,1.429±0.535,respectively.Compared with those of model control group,the scores judged by visual inspection and the pathological scores of healthy control group,sham operation group,omeprazole group and PDTC group were lower,and the differences were statistically significant (t=7.603,7.603,2.909,2.506; t=9.674,9.674,4.277,4.399,all P＜0.05).The serum levels of NF-κB p65 protein of healthy control group,sham operation group,omeprazole group and PDTC group were (68.618±18.450) pg/mL,(77.824±22.228) pg/mL,(106.693±45.312) pg/mL and (103.781± 42.502)pg/mL,respectively; compared with that of model group ((184.882±49.165) pg/mL),which were significantly lower and the differences were statistically significant (t=6.262,5.612,3.308 and 3.427,all P＜0.05).The serum levels of IL-6 protein were (24.826±4.008) pg/mL,(23.599±4.351) pg/mL,(32.370± 11.657) pg/mL and (33.694±10.394) pg/mL,respectively,which significantly decreased when compared with that of model group ((51.378±9.697) pg/mL,t=7.157,7.393,3.546 and 3.392,all P＜0.05).There was no significant difference between PDTC group and omeprazole group in the score judged by visual inspection,pathological scores,the serum levels of NF-κB p65 and IL-6 protein (all P＞0.05).Conclusion NF-κB inhibitor PDTC could reduce the injury severity of esophageal mucosal in reflux esophagitis rat,which mechanism might be related with the down-regulation of NF-κB/1L-6 signaling pathway.