| Research Background:In recent decades,cancer is the main cause of death in most countries in the world,and the incidence and mortality rate of cancer are increasing,among which the proportion of abdominal and pelvic tumors is also increasing year by year。More than 80% of patients with cancer require radiotherapy during their treatment,but the short-term side effects and long-term side effects of radiotherapy are obvious.After the patients’ abdominal-pelvic radiation therapy,about 90% of patients have a change in bowel habits,and more than 50% have acute radiation enteritis,which can be further worsened by concurrent chemotherapy(especially pyrimidine fluoride chemotherapy drugs).Radiation enteritis not only reduces the quality of life of patients,but sometimes has to interrupt the process of radiotherapy,and in severe cases,even threatens the patient’s life.The treatment of abdominal-pelvic cancer and anti-tumor-related toxic side effects requires a lot of human,financial and material resources,which is a great challenge for the country,the family and the individual.At present,there is no standard treatment for radiation enteritis,most of them are symptomatic treatment,symptoms are easy to repeat,and new methods or drugs are urgently needed to improve the efficacy of clinical radiation enteritis.Studies have shown that traditional Chinese medicine has multi-level and multi-target mechanisms in the treatment of gastrointestinal tract,such as antioxidant,anti-fibrosis,promoting intestinal mucosal repair,and anti-inflammatory.Our research group has been clinically using Changhe Decoction to treat radiation enteritis for more than 20 years,and has achieved definite efficacy,and related clinical trial studies have been relatively successful.Previous basic studies have confirmed that the Changhe Decoction have a certain protective effect on the intestinal mucosal cells of radiation enteritis in rats,mainly through anti-inflammatory,antioxidant,inhibition of apoptosis and other mechanisms to protect the intestinal mucosal tissue to treat radiation enteritis,but the specific mechanism and related signaling pathways are not clear.The Nrf2/ANE signaling pathway is a response center for oxidative stress,regulating the transcription of many antioxidant genes and playing a key role in maintaining cellular homeostasis in oxidative,inflammatory,carcinogenic,and proapoptotic environments.In recent years,more and more studies have confirmed that the Nrf2/ANE pathway is also of great significance in the development of radiation enteritis.Research Objective :1.Explore the conditions for establishing a radiation enteritis model,and establish a rat radiation enteritis model with easy operation,reproducibility and stability.2.To explore the effect of Changhe Decoction on radiation enteritis and intestinal mucosal repair,and provide a theoretical basis for clinical application of Changhe Decoction.3.Study the mechanism of action of Changhe Decoction,start from the Nrf2/ANE signaling pathway,explore its influence on the occurrence and development of radiation enteritis,and provide new targets and theoretical basis for the prevention and treatment of radiation enteritis.Research Methods:1.The 20 SD rats with SPF grade were randomly divided into 4 groups,group a: 5 rats with 0 Gy,group b: 5 rats with 8 Gy,group b: 5 rats with 10 Gy,group b: 5 rats with 12 Gy.Except for group a,all the remaining 3groups were given a single irradiation of the whole abdomen(ranging from xiphoid process to anus)using 6MV X-ray linear accelerator at different irradiation doses,and then the general condition of the rats was observed: mental state,feeding and water intake,bowel movements,body weight.After execution,the intestine and colon were retrieved,the pathological changes of the mucosa of the back and colon were observed,and the conditions for establishing radiation enteritis were explored.2.Forty-six SD rats with SPF grade were randomly divided into 4 groups,group A: 10 in normal control group,group B: 12 in model control group,12 in group C: Changhe Decoction group,and 12 in group D: compound glutamine group.Except for the normal control group,the irradiation methods of the remaining three groups were the same,and a 6MV X-ray linear accelerator was used to give rats a single irradiation of the whole abdomen(According to the results of the first part of the experiment,the irradiation dose was 10Gy)to establish a rat injury model of radiation enteritis.Starting from the first day after successful modeling,gastric gavage of different volumes of different solutions was given for a total of 7 days,during which the general condition of the rats was observed: mental state,feeding and water intake,bowel movements,and weight;After execution,the intestine and colon were retrieved and the pathological changes of the mucosa of the back and colon were observed.The kit was used to measure the oxidative stress indexes of intestinal tissues: SOD,MDA,ROS and inflammatory factors: TNF-α,IL-1β,IL-6;Western blotting detected the expression of Nrf2,HO-1,NQO1,Cleaved caspase3,Bcl-2,and Bax in intestinal tissues.Results: 1.Group c rats had diarrhea symptoms,the general condition was poor,and the rats in group c did not die,which was similar to the clinical symptoms,and the modeling was successful.2.1 Compared with group B,rats in group C and D generally had better condition,less pathological damage,and significantly increased body mass on the8 th day after irradiation(P<0.05).2.2 Compared with group B,the contents of Nrf2,HO-1 and NQO1 in the intestinal tissues of rats in groups C and D were increased(P<0.05).2.3 Compared with group B,the contents of ROS and MDA in the intestinal tissues of rats in groups C and D were reduced(P<0.05);SOD activity was elevated(P<0.05).2.4 Compared with group B,the contents of TNF-α,IL-6,and IL-1β in the intestinal tissues of rats in groups C and D were reduced(P<0.05).2.5Compared with group B,the content of Bax and Cleaved-caspase3 in the intestinal tissues of rats in group C and D decreased(P<0.05)and the content of Bcl-2increased(P<0.05).Conclusion1.The irradiation dose of 1.10 Gy can successfully establish a rat radiation enteritis model,which has the advantages of easy operation,reproducibility and stability.2.The Changhe Decoction can improve the symptoms of radioactive enteritis in rats,protect the intestinal mucosa of rats with radioactive enteritis and accelerate the repair of damage.3.The Changhe Decoction plays a role by activating the Nrf2/ARE signaling pathway,on the one hand,enhancing the transcriptional expression of its downstream target genes NQO1 and HO-1,increasing the antioxidant enzyme SOD,reducing the peroxidation products MDA,and enhancing the antioxidant effect;On the other hand,reduce ROS,reduce the expression of related apoptotic proteins,and increase the expression of anti-apoptotic related proteins,including Bcl-2,Bax,Cleaved-caspase3,etc.,thereby reducing the number of apoptosis of intestinal mucosal cells and reducing intestinal damage;At the same time,it inhibits the occurrence of inflammatory reaction,reduces inflammatory factors TNF-α,IL-6,IL-1β,etc.,and improves intestinal symptoms. |
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