| Purpose: To study whether curcumin,a traditional natural medicine,can alleviate the inflammatory damage of gastrointestinal mucosa induced by cisplatin in mice by reg?lating IL-23/IL-17 axis and its related protein STAT3,Bcl-2,TNF-?and JNK signal transduction pathway in MAPK pathway.Material and method:Thirty C57BL/6 male mice aged 6-8 weeks were randomly divided into three groups: blank control group,cisplatin group,curcumin + cisplatin group,10 mice in each group,which were fed in cages and the three groups were carried out at the same time.In this experiment,cisplatin(27 mg/kg)and curcumin(25 mg/kg)were given intraperitoneally.On the first and third day of the experiment,mice in the cisplatin group and the curcumin group were given intraperitoneal injection of cisplatin solution,mice in the curcumin group were given intraperitoneal injection of curcumin solution half an hour before the administration,mice in the blank group were given intraperitoneal injection of normal saline as control,and then mice in the curcumin group were given curcumin injection every other day for 6 days.After 24 hours of fasting water,they were killed and left to be removed Blood and gastrointestinal tissue samples.According to the above groups,the mice were given intraperitoneal injection(IP)of corresponding drugs reg?larly every day.During the experiment,the mice were given free diet water,weighed and recorded the changes of body weight and food intake every day,calc?lated the changes of body weight before and after administration of each mouse and the changes of average daily food intake of each group of mice,and detected the changes of fat and muscle ratio by using the mouse constitution analyzer,To observe the damage of gastric mucosa in mice,calc?late the damage index of gastric mucosa in mice,detect the expression of inflammation and oxidative stress factors in gastrointestinal mucosa damage by HE staining,ELISA and Western blot,and preliminarily explore the possible mechanism of curcumin protecting gastrointestinal mucosa.Statistical analysis: SPSS17.0 software was used for statistical analysis.All values were expressed in the form of mean ± standard deviation(—X±S).The differences between groupswere analyzed by one-way ANOVA.The differences within groups were analyzed by t-test.P< 0.05 means there is statistical difference.Res?lts:1.Self performance and survival state of each group of mice: observe and record the self performance and survival state of each group of mice every day.The res?lts show that the hair of blank control group is glossy,the activity is normal,the diet is normal,and there are no other obvious adverse symptoms.Compared with blank control group,the hair of cisplatin group is d ? ll,sparse,the abdominal hair is obviously off,and the activity is reduced In curcumin group,the hair was glossy,no shedding,the activity increased gradually,and the appetite was improved.2.Weight change of mice in each group: the weight change of mice in each group was detected and recorded every day.The res?lts showed that compared with the blank group,the weight of mice in cisplatin group decreased gradually(P=0.009<0.05),while compared with cisplatin group,the weight loss of mice in curcumin group was significantly improved(P=0.038<0.05),with statistical difference.3.Change of food intake: the change of food intake of mice in each group was detected and recorded every day,and the average food intake of each mouse was calc?lated.The res?lts showed that the daily food intake of mice in cisplatin group decreased(P=0.047<0.05),while the daily food intake of mice in curcumin group was significantly improved(P=0.001<0.05),with statistical difference.4.Physique analysis: the body fat rate(P=0.085>0.05)and muscle content(P=0.482>0.05)of mice in cisplatin group were slightly lower than those in the blank group,but there was no statistical difference,while the body fat rate(P=0.000<0.05)and muscle content(P=0.013<0.05)of mice in curcumin group were significantly higher than those in cisplatin group,There were significant statistical differences.5.Gastric mucosal injury index(UI): after dissection,the changes of gastric mucosa in each group were observed by naked eyes.The res?lts showed that the surface of gastric mucosa in blank group was reddish,smooth and complete,without mucosal congestion,edema,or mucosal damage;the gastric mucosa in cisplatin group was severely damaged,the color ofmucosa was bright red,bleeding spots or flakes appeared on the surface of mucosa,and the damage index was evaluated The score of curcumin group was higher than that of the blank group(P=0.000<0.05),with significant statistical difference;curcumin group had red gastric mucosa,a small amount of congestion,edema and a small amount of bleeding points on the surface of mucosa,and the damage index score was lower than that of cisplatin group(P=0.001<0.05).6.HE staining: for the observation of pathological sections of gastric mucosa,it was found that the structure of gastric mucosa glands in blank group was complete,the cells arranged orderly,the capillaries were rich,the layers were clear and continuous,and no inflammatory cell infiltration was found;the structure of gastric mucosa glands in cisplatin group was not damaged or shed,the arrangement of cells was fair,and no inflammatory cell infiltration was found;the arrangement of gastric mucosa glands in curcumin group was reg ? lar,but no inflammatory cell infiltration was found See infiltration of inflammatory cells.There was no significant difference in the pathological pictures of gastric mucosa among the three groups;for the observation of pathological sections of ileum tissue,it was found that the structure of ileum mucosa gland in the blank group was complete,the tip of villi was complete,the cells were arranged orderly,the capillaries were rich,the layers were clear,and no inflammatory cell infiltration was found;the ileum mucosa in the cisplatin group showed extensive mucosal damage,which was manifested as epithelial exfoliation In curcumin group,there was less gland?lar detachment in ileum,the arrangement of gland?lar was more orderly,the ?lcer of villus tip was obviously improved,the congestion of cells was improved,and inflammation was found The infiltration of disease cells decreased.7.ELISA: compared with the blank group,the levels of IL-17 and IL-23 in cisplatin group were significantly higher,while those in curcumin group were significantly lower than those in cisplatin group(P<0.05).8.Western blot: for the expression of Bcl-2,STAT3,TNF-?and p-JNK in the stomach and ileum of mice,the expression of Bcl-2,STAT3,TNF-? and p-JNK in blank group and curcumin group were significantly lower than that in cisplatin group(P<0.05),but the expression of JNK in the three groups was not statistically different(P>0.05).Conclusion:1.Curcumin has a protective effect on the damage of gastrointestinal mucosa induced by cisplatin in mice.Curcumin has an antioxidant effect and can also reduce the infiltration of inflammatory cells;2.Curcumin can reduce the expression of IL-17,IL-23,STAT3,TNF-?and Bcl-2 in cisplatin induced gastrointestinal mucosal injury model;3.Curcumin can inhibit the JNK/MAPK signal pathway of gastric mucosa in cisplatin induced gastrointestinal mucosal injury model,reduce the phosphorylation of JNK,but has no effect on the expression of JNK protein. |
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