| Objective:Based on the hypothesis of "inflammation-induced angiogenesis",we study the molecular mechanism of ChangRui enema agent in the clinical treatment of radiation proctitis from the NF-κB and VEGF signaling pathways,to provide new drug targets and research ideas for the clinical treatment of radiation proctitis.Methods:We used C57/BL mice to linear accelerator single irradiation 27 Gy to establish radiation proctopathy mouse model.Then we used 7.2g/Kg、3.6g/Kg、1.8g/Kg of ChangRui enema agent of high,medium and low three doses to cure them.respectively set Enema with dexamethasone combined with gentamicin and bawei xilei powder as positive control groups.Killing test after 2 weeks of continue enema.Mice were observed for general condition and feces during this period.We will do rectal tissue HE staining to confirm the pathological changes of radiation proctitis,at the same time by immunohistochemistry 、PCR and ELISA detection,we want to explore the relationship between the expression of NF-κB,VEGF and PKA in rectal tissues and serum of mice with radioactive proctitis.Results:1.The effect of ChangRui enema on rectal histopathology of radiation Proctitis C57/BL Mice(1)Compared with the normal blank group(P <0.05),the mucosal lesions of the mice were significantly different after the irradiation,and the model was successful.(2)Compared with the model group(P﹥0.05),there was no significant difference between the degree of rectal mucosal injury in the treatment group and the Chinese medicine control group.Compared with the western medicine positive control group(P<0.05),the high and middle dose groups were superior to those mice.(3)The difference was statistically significant(P <0.05),indicating that the efficacy ofhigh-dose intestine enema was better than that of the control drug dexamethasone plus gentamicin and the control Chinese medicine Bawei tin powder scattered.Compared with the low dose group(P <0.05),the difference was statistically significant,indicating that the treatment of radioactive ileitis high dose of intestinal enema efficacy is better than low-dose drugs.2.The effect of ChangRui enema on the expression of NF-κB 、VEGF in rectal tissues was analyzed by immunohistochemistry(1)The blank control group also see a small amount of NF-κB,VEGF expression,consider with the enema device stimulation,can be ignored.The expression of NF-κB and VEGF was obvious in each group after irradiation,but there was significant difference compared with blank group(P <0.05).Indicating that NF-κB,VEGF expression is caused by radiation stimulation of rectal mucosa.(2)Compared with the model group(P <0.05),the difference was statistically significant between the cure groups,indicating that the intestine group,dexamethasone celebration group and Bawei tin group were able to inhibit the expression of NF-κB and VEGF.There was significant difference between the high-dose group and the western medicine control group(P <0.05).The difference was statistically significant(P <0.05)between the high/middle-dose group and the Chinese medicine control group.The results showed that the high dose of intestine enema could significantly down-regulate the expression of NF-κB and VEGF in rectal tissue of radiation-induced colorectal,and the middle-dose group which was not sure superior to that of western medicine.3.The effect of ChangRui enema on the expression of NF-κB、VEGF in rectal tissue was detected by PCR.(1)The results showed that the expression of NF-κB and VEGF in the blank control group was negligible,and the expression of NF-κB and VEGF in the other groups were different,Compared with the blank group,the difference was statistically significant(P<0.05),suggesting that the normal rectal mucosa of the normal or not express NF-κB,VEGF,rectal mucosa by irradiation to stimulate the occurrence of NF-κB,VEGF gene expression change.(2)The expression of NF-κB and VEGF in the model group was significantly higher than that in the other groups(P <0.05),indicating that there was a change in the expression of NF-κB and VEGF in the other groups.(3)Compared with the western medicine control group and the traditional Chinese medicine control group,the difference was statistically significant(P <0.05)in the high/middle-dose group on the expression of NF-κB and VEGF,indicating that the highand middle dose group Significantly down-regulated the expression of NF-κB and VEGF in rectal colorectal goiter,which can control inflammation and inhibit angiogenesis.4.The effect of ChangRui enema on the content of protein kinase A(PKA)in serum was determined by ELISA(1)The difference between the control group and the treatment group was statistically significant(p <0.05),suggesting the model was successful.(2)The difference between the the blank control group and the other groups(except for the high-dose group),was statistically significant(p <0.05),but there was no significant difference between the high dose group and the blank control group(p> 0.05).(3)Compared with the positive control group and The high dose group,the difference was statistically significant(P <0.05).But there was no significant difference between the positive control group and The middle/low-degree dose groups(P> 0.05).Indicating that the high dose of intestinal group can significantly inhibit the protein kinase A(PKA)content.Conclusion: Changrui enema can rapidly improve the general condition of mice with radiation proctitis,restore the eating and body weight in time,protect and repair the intestinal mucosa in time,promote ulcer healing,can significantly improve the pathological changes under light microscope and structural abnormalities.The expression of IL-1β and NF-κB was down-regulated by enteritonin,which could inhibit the expression of VEGF and control the inflammation,stop bleeding and promote the repair of intestinal mucosa,and confirm the inflammation-induced angiogenesis hypothesis.The High dose of intestinal enamel enema treatment of radioactive ileitis in mice with significant effect. |
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