| Purpose: To explore the protective effect of baicalein on gastric mucosa injury induced by cisplatin,and to elucidate its possible mechanism of action,so as to provide the necessary theoretical basis and experimental basis for the clinical application of baicalein in the future,especially for the reduction of gastrointestinal side effects of cisplatin.Material and method: 30 healthy male C57 mice(18-22g)were randomly divided into 3 groups: control group,cisplatin group,cisplatin + baicalein group,10 mice in each group,fed in cages with free diet and water.The control group was given intraperitoneal injection of normal saline for 6 days,cisplatin group,cisplatin 27 mg / kg,once respectively on the first and fourth days of the experiment.The dosage and method of cisplatin in baicalein group were the same as that in cisplatin group,and baicalin 50 mg / kg was injected intraperitoneally for 6 consecutive days.After the injection on the sixth day,all groups of animals were put to death after fasting food and water for 24 hours,leaving the blood and the complete stomach tissue of mice.From the beginning of administration to the time of execution,weigh and record the weight of each group of mice every day,calculate the weight increase and decrease value of each mouse before and after administration,observe the gastrointestinal mucosa damage of mice,calculate the gastric mucosa damage index of mice,detect the expression of related inflammatory factors and their proteins in the gastric tissue and blood of mice by HE staining,ELISA and Western blot.Results: The general observation results showed that the control group mice had normal mental state,smooth coat,active activity,active foraging,dark brown feces particles,and no other symptoms;the cisplatin group mice had mental depression,reduced food intake,decreased activity,hair lusterless and sparse fall off,loose stool,irritable,irascible,and biting cage symptoms;the spirit of mice in baicalein group was better than that in cisplatin group,with no significant decrease in activity,no obvious shedding and luster of hair,no obvious loose stool.Compared with the control group,the weight of mice in cisplatin group was significantly reduced,while that in baicalein group was improved(p<0.05);in the control group,the mucosal surface was light red,smooth and complete,without hyperemia,edema,damage,bleeding point,capillary dilation;in cisplatin group,gastric distention and gas can be seen,a large amount of food remains can be found,gastric mucosa is seriously damaged,showing bright red,local lesions,redness and swelling,a small amount of bleeding points can be seen on the surface of mucosa,and the damage index score is higher than that in the control group(p<0.05);there was no obvious food residue and flatulence in the stomach of baicalin group.Compared with cisplatin group,the pathological changes of gastric mucosa in baicalin group were alleviated.The mucosa is pink,intact without damage,without obvious punctate hemorrhage.The damage index score of baicalin group was lower than that of cisplatin group(p<0.05).In the control group,the glandular structure of gastric mucosa was complete,the cells were arranged orderly,the capillaries were rich,the layers were clear and continuous,no inflammatory cell infiltration was found;in cisplatin group,the glandular structure of gastric mucosa was destroyed,most of them were exfoliated,the cells arranged disorderly,the blood vessels were ruptured and a large number of red blood cells were infiltrated,and inflammatory cells were infiltrated under the mucosa;in the baicalin group,the gastric mucosa glands were intact or occasionally exfoliated,the arrangement of glands was relatively complete,no red cell infiltration was found,a small number of capillaries were damaged,and inflammatory cells were significantly reduced compared with cisplatin group;compared with the control group,the expression of IL-1 β,IL-6,IL-8,TNF-α in cisplatin group was significantly higher than that in cisplatin group,After baicalein treatment,the expression of IL-1 β,IL-6,IL-8,TNF-α was significantly lower than that of cisplatin group,the difference was statistically significant(p<0.05);and compared with the control group,the content of Caspase3,Caspase9,p53,Bax in cisplatin group was significantly higher than that in the control group,and the baicalin group was lower than that in cisplatin group but higher than that in the control group(p<0.05),and the expression of Baicalin in Bcl-2 protein in the baicalin group and the control group were higher than that in cisplatin group(p<0.05);there was no significant difference among the three groups on the expression of p38(p>0.05),but the expression of p-p38 protein was significantly higher than that of the control group.After treatment with baicalein,the expression of p-p38 was significantly lower than that of cisplatin group(p<0.05).Conclusion: Baicalein can inhibit the expression of IL-1 β,IL-6,IL-8,TNF-α induced by cisplatin;baicalein can regulate the apoptosis of gastrointestinal mucosa cells induced by cisplatin by inhibiting the expression of Caspase3,Caspase9,p53 and Bax / Bcl-2 imbalance;baicalein can down regulate p38 MAPK pathway,inhibit the phosphorylation of p38 MAPK pathway,and alleviate cisplatin induced gastrointestinal mucosal damage. |
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