The Protective Effects And Mechanisms Of The Compound Matrine On Small Intestine In Acute Radiation Enteritis

Objective: Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed to the abdomen or pelvis. The aim of this study was to set the role of compound matrine in acute actinic enteritis prevention and to provide the experiment evidence for compound Matrine injection in clinical treatment of acute radiation enteritis.Method: Fouty-two male Sprague-Dawley rats were used in the study . The rats were divided into four groups. GroupⅠ(n =6): normal rats and isotonic saline without abdominal irradiation(sham control group); GroupⅡ(n =12): abdominal irradiation irradiation(10 Gy) and isotonic saline ; GroupⅢ(n =12): abdominal irradiation(10 Gy) and high dose compound matrine injection (2ml/kg) for seven days following irradiation; GroupⅣ(n =12): abdominal irradiation and low dose compound matrine injection (0.4ml/kg) for seven days following irradiation. Irradiation consisted of 6MV X-rays at single dose of 10Gy which source skin distance is 100cm to the abdominal region of the animals anaesthetized with sodium thiopental 40 mg/kg intraperitoneally. Changes of general appearance of rats was observed. Eight days after irradiation, all the animals were sacrified with lethal dose sodium thiopental. The small intestine were removed and washed with isotonic saline solution and samples of the terminal ileum were fixed in buffered formalin for histopathological examination. The terminal ileum were analyzed for morphological changes. Nitrate reductase activity assay were performed to measure the NO content by used of homogenate of terminal ileum. Results:1.Changes of general appearance was observed in each group. It was showed that rats in groupⅠhave a good appetite and response, body hair are smooth and shiny, weight gain. The rats in groupⅡare Listlessness, significantly loss of appetite, unresponsive, obscure body hair. The rats in groupⅢandⅣafter receiving X-ray irradiation show the symptom of losing the appetite in the first three days, then recover to normal , especially the rats in groupⅢ.2.The stool of each group rats were observed. The results showed that the stool of groupⅠis shaped and grainy. Three days after acute irradiation a number of rats developed diarrhea. None of the rats died. For example:The stool was watery and mucous and have undigested food residue,be etc. However, we found that compound matrine injection could relief the symptom of diarrhea. There are more rats in groupⅡhave long time diarrhea than rats in groupⅢandⅣ.3. The rats'weight Changes in each group. The 8 day,All rats receiving irradiation had weight loss compaire with the groupⅠ, but the compound matrine treatment group(GroupⅢandⅣ) had smaller weight loss than GroupⅡ. Rats receiving compound matrine injection following irradiation recovered weight, and high does compound matrine group presented better results than the low does compound matrine group. However, rats in groupⅡwhich receiving irradiation only did not recover weight. There was significant difference in the weight of rats in groupⅡ(210.33±21.71g)as compared with the groupⅠ(276.83±18.68g)(P<0.001). There was no significant difference in the weight of rats between groupⅢ(269.33±17.70g) and groupⅠ(P>0.05). However, there was difference in weight between groupⅣ(254.50±14.87g)and groupⅠ(P<0.05).4.The terminal ileum were analyzed for morphological changes. The changes of terminal ileum mucosa were evaluated for mean villous height and number of villous per unit by micrometer adopted light microscope. Ileal villous number and villous height decreased following irradiation. The epithelial layers of the villous were significantly reduced in groupⅡrats(51±8) compared to sham group(77±8) (p <0.001). Further more, the mean villous height were significantly reduced in groupⅡrats(196.24±27.64μm) compared to sham group(287.20±30.87μm) (p<0.001). However, the mucosal structure was preserved in the compound matrine treatment group in a dose-dependant manner. The results showed that High dose compound matrine injection following irradiation significantly prevented decrease in ileal villous number(74±10) and villous height(283.88±47.17μm), which showed no significant difference compared to sham group(77±8 and 287.20±30.87μm, respectively(P>0.05).5.Intestinal NO concentration was detected by nitroreductase assay. In irradiated rats, intestinal NO concentration was found to be increased significantly compared to sham group. The intestinal NO concentration in groupⅠ,Ⅱ,Ⅲand groupⅣis 0.25±0.03, 0.55±0.09, 0.26±0.02 and 0.28±0.06μmol/g, respectively. There was significant difference in intestinal NO concentration between groupⅡand the other groups(P<0.001). The intestinal NO concentration of low dose compound matrine treatment group(groupⅣ) is slightly higher than in the sham control group (groupⅠ)(P<0.05). However, there was no significant difference in intestinal NO concentration of high dose compound matrine treatment group(groupⅢ) compared to the sham control group(groupⅠ),This data indicated that compound matrine treatment could decrease intestinal NO concentration in a dose-dependant manner.Conclusion:1. The Compound Matrine could relief the gastrointestinal tract reaction and reduce the pathomorphological changes of intestine in acute radiation enteritis rats, as well as repair the intestinal mucosa.2. The Compound Matrine could relief the gastrointestinal tract reaction. Its mechanism may act as reducing the intestinal NO concentration.3. Compound Matrine treatment could prevent experimental acute radiation enteritis in rats in a dose-dependant manner.As to this point,further reserch is needed.