| Objective: To establish a stable canine model of acute ulcerative colitis and evaluate the clinical efficacy of trial-produced Ento-Ⅰ colon-soluble capsules for treating acute ulcerative colitis in dogs.Method:1.The establishment of acute colitis modelSixteen healthy dogs were randomly divided into control group and 3 different concentrations of acetic acid group,4 in each group,male and female.After anesthesia was injected with QMB,the acetic acid group was infused with 4%,7% and 10% acetic acid(2mL/kg)respectively.The control group received no anesthesia,and the corresponding dose of sterile physiological saline was directly perfused through the rectum;the first day and the third day after the administration.After 7 days,observe the defecation situation of each group,and observe the degree of damage of colon mucosa of experimental dogs with electronic endoscopy;sacrifice the experimental dogs on the 7th day,and take the diseased colon for tissue section observation.2.Method of administrationSixteen adult dogs of the same strain were randomly selected and divided into a model group,a normal dose group of Ento-Ⅰ colonic capsules,a 2 dose group of Ento-Ⅰ colonic capsules,and a positive drug group.Sulfasalazine dissolved in the colon),4 in each group,male and female.Fasting administration,the model group was fed 2 capsules/kg body weight of starch colonic dissolve capsules,the normal dose group was fed with Ento-Ⅰ colon soluble capsules 2 pellets/kg body weight,twice the dose group was given 4 pellets/kg body weight,positive drugs The group was fed with sulfasalazine and 2 capsules/kg body weight.All experimental animals during the trial were housed in single cages and provided the same amount of food and drinking water daily.3.Laboratory testing indicators and efficacy judgmentThe number of blood cells,complete set of biochemical indicators,C-reactive protein,and statistical analysis data were measured on the day before and 1 d,3 d,and 7 d afteradministration.At 1 d,3 d and 7 d after administration,the damage of the colonic mucosa of the experimental dogs was observed with an animal-specific endoscope,and the occult blood status of the feces was also checked at the same time.After 7 days,the experimental dogs of each group were dissected,colon tissue was fixed,pathological sections were made to observe the degree of colon damage,and mucosal injury scores were performed.According to the fecal traits,fecal occult blood,endoscopic observation and laboratory examination,comprehensive determination of the efficacy of Ento-Ⅰ colon dissolve capsule on canine acute colitis.Result:1.Animal models of acute colitis: Dogs infused with 4% acetic acid showed transient loose stools,and only slight inflammatory cell infiltration was observed in pathological sections.Dogs infused with 10% acetic acid had too strong inflammatory responses leading to intestinal perforation and death;The 7% acetic acid in dogs,fecal traits,and colon endoscopy all showed obvious symptoms of colitis.Three days later,ulcer lesions appeared.Seven days later,ulcer lesions were detached.Histological examination revealed that there were obvious inflammatory cells around the ulcer lesions.Infiltration,inflammatory cell infiltration is significantly reduced over time,and fibroblasts proliferate.The results showed that rectal infusion of 7% acetic acid can successfully induce canine acute ulcerative colitis.2.Ento-Ⅰ colon dissolve capsule treatment of acute colitis in dogs:Clinical observation results: 1 day after administration,the experimental dog was irritated and restless,frequently looked back at the abdomen,and a small part bite the dog’s cage with a mouth,giving a painful cry,urgency,and weight,endoscopic examination of the colon mucosa for unevenness,mucosal bleeding,edema,and spotting.Shaped erosions and ulcers;3 days after administration,the Ento-Ⅰ colonic capsulose double-dose group,the stool became a paste,occult blood test was strongly positive,endoscopic examination of the colon mucosa edema reduced,ulcers decreased;after administration On the 7th day,the stools were basically formed without blood.The occult blood test was positive.The colon mucosal exudate was absorbed by endoscopy,the color of the intestinal mucosa became pale,and the normal luster of the mucosa was not completely restored.However,the surface of the colonicmucosa was smooth.C-responsive protein(CRP)results: One day after the model was established,the CRP was 103.775 ± 16.747 mg/L,and then decreased gradually with the extension of time,reaching 36.425±8.764 mg/L on the 7th day.On the 7th day after administration,the CRP of Ento-Ⅰ colonic capsules was 18.450 ± 7.303 mg/L and 7.975 ± 2.425 mg/L in the normal dosage and double-dose group,respectively.The CRP in the positive drug group was 14.500±2.783 mg/L,indicating that : CRP returned to the normal range after twice the amount of Ento-Ⅰ colon-soluble capsule treatment,and the difference was significantly lower than the normal dose group and positive drug group at this time.On the 7th day after administration,the total number of white blood cells in the double-dose group and the positive drug group decreased to the normal range,and the double-dose group was 10.600 ± 2.688.The difference was extremely significant when compared with the normal dose group and the positive drug group.During the test period,all the biochemical indicators except urea nitrogen of the experimental animals were normal,that is,the test drugs had no effect on the liver and kidney function of the test dogs.Observe the histological sections 3 days and 7 days after administration.In the double-dose group,on the 3rd day after administration,there was an ulcerous lesion in the colonic mucosa and infiltration of inflammatory cells,but on the 7th day after administration,the ulcer lesions disappeared,the number of inflammatory cells decreased,and fibroblasts proliferated.Two doses of Ento-Ⅰ colon-coated capsules could repair the ulcerative surface of acute colitis.In the normal-dose group,3 days after administration,there was a large number of focal ulcers in the mucosa,and a large number of inflammatory cells infiltrated into the muscular layer.Cells increased;7 days after administration,intestinal mucosal epithelial cells were swollen and inflammatory cells were reduced,indicating that inflammation has not disappeared.In the positive drug group,3 days after administration,focal ulcers appeared in the mucosal layer as in the normal dose group,and a large number of inflammatory cells infiltrated into the muscle layer.7 days after administration,inflammatory cell ulcer lesions were reduced,and the intestinal mucosa was epithelial The swelling of the cells indicates that the inflammation has not been completely repaired.Conclusion:1.An ideal stable canine model of acute ulcerative colitis can be produced using 7%acetate rectal infusion for 15 s.2.During trial 7d,the trial Ento-Ⅰ colon dissolve capsule treatment of acetic acid-induced canine acute ulcerative colitis is affirmative,its effect is better than the normal drug dose group and the positive drug sulfasalazine group.3.During trial 7d,the doubled dosage of the trial Ento-Ⅰ colonic capsule did not cause damage to the liver and kidney functions of the dog. |
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