肠缺血再灌注后应用抗组胺药对大鼠生存率的影响

目的： 在肠缺血再灌注后静脉给予抗组胺药酮替芬，观察它对SD大鼠小肠功能结构以及存活率的影响。方法： 72只SD大鼠随机分为3组：S组（假手术组）、M组（模型组）、K组（缺血再灌注＋酮替芬1 mg/kg组），每组又分术后3 d、7 d两亚组。复制小肠缺血/再灌注模型，K组在再灌注前5 min和再灌注后3 d静脉注射酮替芬。观察各组大鼠3 d（S3,M3,K3）、7 d（S7,M7,K7）的存活率、存活状态，检测小肠组织组胺浓度，观察肠黏膜病理结构变化和肠黏膜肥大细胞（intestinal mucosal mast cell，IMMC）超微结构及类胰蛋白酶表达比较。结果： M3组、K3组存活率低于S3组（P<0.05）； M7组存活率低于S7组（P<0.05），K3组与M3组、K7组与S7组存活率差别无显著（P>0.05）。K7组存活率高于M7组（P<0.05）。M组、K组肠黏膜绒毛损伤轻微。电镜示M组微绒毛肿胀脱落，K组微绒毛不齐；S组IMMC超微结构正常，M组脱颗粒现象明显，K组次之。各组间肠黏膜Chiu’s评分、IMMC计数及类胰蛋白酶表达比较均无显著差异（P>0.05）。K7组肠组织组胺浓度低于S7组和M7组（P<0.05）。 结论： 肠缺血再灌注后应用抗组胺药酮替芬能改善大鼠小肠黏膜结构并增加大鼠生存率，IMMC活化脱颗粒组胺释放可能不利于肠缺血再灌注损伤大鼠的长期生存。

Effects of ketotifen administered after intestinal ischemia reperfusion on the survival rate in rats

AIM: To investigate the effect of antihistaminic, ketotifen, administered for three days after intestinal ischemia reperfusion (I/R), on survival rates in SD rats. METHODS: The intestinal I/R model of SD rats was set up with clamping the superior mesenteric artery for 75 min. 72 SD rats were divided into 3 groups: group S for sham group, group M for model group, group K for ketotifen treatment (model + ketotifen 1mg/kg), each group was divided into 2 sub-group: 3rd d and 7th d (eg: group S3, S7, M3, M7, K3, K7; n=12 per sub-group). Ketotifen was administered via caudal vein 5 min before reperfusion in group K, while normal saline was administered in groups S and M and was kept on administering once a day for 3 days after reperfusion. The survival rates were recorded at 3 d or 7 d after operation. The morphological changes of intestinal mucosal and mast cells were observed under light and electron microscopes in survival rats. The concentration of histamine was also determined in the intestinal samples. RESULTS: The survival rate at 3rd d in group M and K was lower than that in group S (P<0.05 or P<0.01). No significant difference of the 3rd d survival rate between group K and M was observed (P>0.05). The survival rate at 7th d in group M7 was lower than that in group S7 and K7 (P<0.05), no significant difference between group K7 and group S7 was found (P>0.05). Light and electron microscope examinations showed slight damage of intestinal mucosal in group M and K in survival rats, while the result in group S was almost normal. Mast cell degranulation was obvious in group M7, partly in group K while none was found in group S. There was no significant difference in Chiu’s score, the expression of tryptase and the number of IMMC among the groups in the survival rats (P>0.05). The concentration of histamine in the intestine in group K7 was lower than that in group S7 and M7. CONCLUSION: Ketotifen administered after intestinal ischemia reperfusion increases the survival rate in rats. The mucosal mast cell degranulation and release of histamine may be adverse to the prognosis of intestinal ischemia reperfusion injury in rats.