The Clinical Observation And Experimental Research Of Radioaction Injury To The Stomach And Duodenum

The incidence of malignant tumors of the pancreas increasing, seriously endangerthe lives of patients. Due to pancreatic cancer occult and early symptoms, treatment inpatients with advanced, surgical resection rate was only14.2%,most patients wereunresectable. Pancreatic cancer is not very sensitive to chemotherapy, so radiationtherapy become an important means of treatment of pancreatic cancer. Radicalradiotherapy for pancreatic cancer in addition to considering the tumor radiobiologyfactors, but also a full assessment of radiotherapy may endanger the surrounding normaltissues and organs and functions. Radiation therapy is not only to achieve the Bureau ofpancreatic cancer control at the same time to reduce the tumor surrounding normaltissue radiation injury. Due to the anatomical relationship of the pancreas, stomach andduodenum, pancreatic cancer radiation therapy inevitably damage on the stomach andduodenum. The past radioactive gastroenteritis research concern in the jejunum andileum and colorectal, is based on traditional radiotherapy for rectal cancer, prostatecancer and gynecological tumors.Currently, the report of radition injury and treatmentresearch on stomach,duodenum is less. Reported in the literature of radiation enteritishave a close relation with cytokines IL-6, IL-1and TNF-alpha. Our previous studies andreported in the literature that pancreatic cancer patients in an early stereotacticradiotherapy the gastrointestinal reactions up to70%, acute gastroduodenal mucosalerosion and ulceration of7%, the late gastric ulcer and obstruction were17%,9%.Based on the above background, we preliminary observing endoscopic gastric andduodenal mucosal damage in six pancreatic cancer patients who have received radiationtherapy, while observing the improvement of the clinical symptoms after givenacid-suppressing drugs and gastrointestinal mucosal protective agent. Six patients with pancreatic cancer showed a grade Ⅲradiation enteritis, manifested as abdominal pain,diarrhea, nausea, vomiting with melena. Gastroscopy examination showed a grade IVradiation injury,manifested as the mucosa of duodenal and duodenum hyperemia,edema, ulceration, surface covered with white fur. The clinical symptoms wereimproved after given the antacid famotidine and gastrointestinal mucosal protectiveagent Almagate Suspension. Preliminary observations indicate that the stomach,duodenum radiation injury is an important complication of pancreatic cancerradiotherapy, seriously affecting the quality of patients life.In order to have a furtherobservation on the radiation injury of stomach, duodenal mucosa and the protectiveeffect antacid famotidine and the gastrointestinal mucosa protective agent Almagatesuspension on the stomach, duodenal mucosa, we have established an animal model ofstomach, duodenum radiation injury which can provide a theoretical basis for clinicalprotection stomach, duodenum radiation injury.Objective:1.Established a mouse model of acute radition enteritis which closer toclinical.2.Investigated the efficacy and repair mechanisms of acid-suppressing drugsfamotidine joint gastrointestinal mucosa protective agent Almagate Suspension after the60CO-ray radiation injury to the stomach, duodenum.Provided new theoretical andexperimental basis for the two drugs intervention in the treatment of gastric andduodenal radiation injury.Methods:1.Established a mouse model of acute radition enteritis93Balb/cfemale mice were randomly divided into seven groups as control group,4.5Gy group,6Gy group,9Gy group,12Gy group,13.5Gy group and15Gy group.For eachgroup,mice were sacrificed at3.5,7days after single abdominal irradiation of60CO,respectively. Observed the normal circumstances of mice,such asmental,activity,stool,weight,evalue of health status in mice with activity score.Take thestomach, duodenum tissue fixed,embedding,sliced,HE staining,observed mucosalstructure under light microscopy.Take spleen and mesenteric lymph nodesgrinding,extraced total mRNA,reverse for cDNA,Realtime PCR method was used todetect the change of inflammatory factor IL-6,IL-1β，TNF-α. Detect the change ofinflammatory factor IL-6,IL-1β，TNF-α in serum by ELISA method.2.On the basis ofthe model of acute radiation enteritis given famotidine and Almagate suspension,observe the protective effect on the stomach, duodenum radiation injury.78Balb/cfemale mice were randomly divided into four groups as group A,control group:irradiation and drug intervention, group B, the blank drug intervention group: irradiation, drug intervention, famotidine0.5ml/only, Almagate suspension0.3ml/ig only, groupC, irradiated group:12Gy60COray single abdominal irradiation+saline0.8ml/igonly,group D, irradiation, drug intervention group:12Gy60COray single abdominalirradiation and drug intervention, famotidine0.5ml/only, Almagate suspension0.3ml/only orally. All the intervention groups were given drug or saline from two days beforeirradiation, to the end of the first3.5days after irradiation, For each group,mice weresacrificed at3.5days after single abdominal irradiation of Cobalt-60,respectively.Takethe stomach, duodenum tissue fixed,embedding,sliced, HE staining,observed mucosalstructure under light microscopy.Use improved Chiu’s score evalue the degree ofintestinal mucosal injury.Take spleen and mesenteric lymph nodes grinding,extracedtotal mRNA,reverse for cDNA,Realtime PCR method was used to detect the change ofinflammatory factor IL-6,IL-1β，TNF-α of spleen and mesenteric lymph nodes. Detectthe change of inflammatory factor IL-6,IL-1β，TNF-α in serum by ELISA method.Result：1. Single12Gy60COabdominal irradiation,mice duodenum pathologicalmanifestations comply with the requirements of radiation enteritis animals intestinalmucosal injury. Real-time PCR was used to detect the spleen, mesenteric lymph nodesof inflammatory factors IL-6, IL-1β, TNF-α expression,and its expression wereincreased (P <0.05), Detected by ELISA in peripheral blood serum inflammatory factorsIL-6, IL-1, TNF-alpha, and its expression were increased (P <0.05). symptoms aretypical and the mortality rate is low,to successfully establish the mouse model ofirradiated enteritis Single12Gy60COabdominal irradiation is optimum.2. On the basisof the model of acute radiation enteritis given famotidine and Almagatesuspension,drug intervention group comparised with irradiated group has a lessweight loss.Realtime PCR method was used to detect the change of inflammatory factorIL-6,IL-1β，TNF-α of spleen and mesenteric lymph nodes,its expression in drugintervention group is lower than in the radiation group, IL-6, IL-1beta expression has asignificant difference between drug intervention group and irradiated group wasstatistically significant (P <0.05). Detect the change of inflammatory factor IL-6,IL-1β，TNF-α in serum by ELISA method, its expression in drug intervention group is lowerthan in the radiation group was statistically significant (P <0.05).Observe the length ofvilli and the depth of crypt under light microscope, villus height in drug interventiongroup is higher than radiation alone group (P <0.05). crypt depth in drug interventiongroup is deeper than the irradiated group (P <0.05) deep. Conclusion:1. Successfully established the mouse model of irradiatedenteritis.In the model, cytokines IL-6, IL-1beta, TNF-alpha expression in spleen,mesenteric lymph nodes and peripheral blood serum were significantly increased (P<0.05).2. The famotidine and Almagate of suspension, can significantly reduce theexpression of inflammatory factor IL-6, IL-1beta, TNF-alpha radiation of mousespleen, mesenteric lymph nodes and peripheral blood serum,it also can reduce theradiation injury of mouse duodenal mucosa.