| ObjectiveThis study aims to investigate the mechanism of Chinese medicated food Qi Yao Ji Jin Zhou for regulating the tight junction proteins expression in 5-FU induced gastrointestinal mucositis from the aspect of TLR4/NF-κB singnal pathway.To observe the changes of weight and spleen deficiency symptom scores in rats during the entire experiment period;and to evaluate the treatment effect and dose-effect relationships of different doses of medicated food on 5-FU induced gastrointestinal mucositis in rats.MethodsThis study was an experienmental study design.Forty SPF Wistar rats were randomly assigned to five different study groups which included model group,high-dose intervention group,middle-dose intervention group,low-dose intervention group and control group,and 8 rats were included in each group.The entire study durations were 16 days.On day 1,rats in different dosages groups and model group were injected with 5-FU at 150 mg·kg-1 to reproduce the model of chemotherapy-induced gastrointestinal mucositis,and the control group was injected with NS at the same dose.On day 2-15,The model group and control group were treated with rice porridge 10m·kg-1,and rats in low-dose group,middle-dose group and high-dose group were treated with Qi Yao Ji Jin Zhou 5ml·kg-1、10ml·kg-1 and 20ml·kg-1,respectively.The weight and spleen deficiency symptoms of each group were observed and recorded daily.Sample tissues of the rats were collected on the last day of experiment to investigate the level of expression of channel proteins(TLR4,NF-κBp50,NF-κBp65,and IκBα)and intestinal tight junction proteins(Occludin,Claudin-1,JAM-1,and ZO-1)by ELISA approach.Intestinal mucosa and gastric mucosa were taken for pathologic examination by hematoxylin-eosin staining.XFuor4 software was used to process data of ELISA,and statistical software SPSS 20.0 was applied for data analysis.Results1 Change in the expression of intestinal tight junction proteinsDifferences in the expressions of Claudin-1,JAM-1 and ZO-1 among groups were all statistically significant(P<0.05)except Occludin(P>0.05).The changes of Claudin-1 in the three intervention groups and the control group were higher than that in the model group,and the level of Claudin-1 was highest in the control group,and the changes among the three intervention groups with different dosages of medicated food showed no significant change(P>0.05).The expression of JAM-1 in the model group was lower than that in the intervention groups and the control group,and the expression in thecontrol group was identified to be the highest.There was no significant change among the intervention groups,the model group and the control group regarding to the expression of ZO-1(P>0.05).2 Change in the expressions of channel proteinsDifferences in the expressions of IκBα and TLR4 among groups were statistically significant(P<0.05)except NF-κBp50 and NF-κBp65(P>0.05).The expression of IκBα in the model group was higher than that in the middle-dose group and the low-dose group,and the expression in the middle-dose group was lowest in all groups.The IKBa changes among the three intervention groups with different dosages of medicated food showed no significant change(P>0.05).The expression of TLR4 in the model group and the intervention groups were higher than that in the control group,and the TLR4 expression in the model group was the highest in all groups.The TLR4 changes among the three intervention groups with different doseages of medicated food did not show any significant change(P>0.05).3 Gastric mucosa and intestinal mucosa pathomorphologyThe gastric mucosa villus among all the groups were almost completed,and the edges of villus were smooth.However,the degree of congestion among the groups were somewhat different,with the most serious situation identified in the model group distributions of red blood cells were relatively dense in villus,and capillary congestions were detected in lamina propria.There was no obviously difference in gastric mucosa change among the three intervention groups,and the level of capillary congestion was found to be the lowest in the control group.The change of intestinal mucosa pathomorphology among groups did not reach statistical significance(P>0.05).However,the morphology of the intestinal mucosa among groups was shomewhat different,with the damage of the intestinal mucosa was most serious in model group the intestinal villus degenerated or atrophied,and part of the intestinal villus was dropped.The damage in the low-dose group was better than that in the model group.The intestinal villus was irregular,sparse and swelling in the middle-dose group.Status of the intestinal villus in the high-dose group was better than that in the middle-dose group,and it was more or less similar to that in the control group.4 Change of the spleen deficiency symptom scoresAfter chemotherapy,all rats showed spleen deficiency symptoms except the control group,such as tired body,deciduous hair and diarrhea,which proved the successful copy of spleen deficiency symptoms rats model.Scores began to increase from day 2 after chemotherapy in all groups,and the scores in the control group was found lower than that in other groups,and it was the highest in the model group.The changes of the symptom score in the control group were steady.5 Change of body weight in ratsWeight of rates in all groups significantly decreased from day 2 to day 7 except control group,and the lowest point of weight was identified from day 5 to day 6.Rat weight in the high-dose group was better than that in the model group.In this study,the trend of weight in control group increased gradually,and it was higher than all the other groups.ConclusionQi Yao Ji Jin Zhou medicated food has a positive impact on the expressions of tight junction proteins of Claudin-1 and JAM-1,but the impacts on Occludin and ZO-1 are still unclear.Qi Yao Ji Jin Zhou medicated food can depress the expressions of IKBα,but the role in NF-κBp50,TLR4 and NF-κBp65 needs further investigation.It is not clear whether the effect of the medicated food was worked through the TLR4/NF-κB singnal pathway.In conclusion,Qi Yao Ji Jin Zhou medicated food can repaire the damage of intestinal mucosa and gastric mucosa in a certain degree,and it has a positive effect in controlling weight and spleen deficiency symptom scores in rats after chemotheraphy. |
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