不同时间四氢叶酸钙解救对大剂量甲氨喋呤化疗导致的大鼠肠黏膜损伤保护作用的研究

The different time rescue of calcium 5-formyltetrahydrofolate for protecting enteral mucosa damage by chemotherapy of high-dose methotrexate in rats

目的观察不同时间四氢叶酸钙(CF)解救对大剂量甲氨喋呤(HD-MTX)化疗导致的大鼠肠黏膜组织形态学的改变、病死率及腹泻情况,探讨CF使用的适宜时机。方法6周龄Wistar大鼠分5组。A组:正常对照组;B组:空白对照组;C、D、E组:实验组,分别于腹腔注射HD-MTX后12、24、30h予以CF解救。观察各组大鼠病死率、腹泻情况及空肠大体形态,标本测肠黏膜绒毛长度和隐窝深度。结果A组无腹泻,B、C、D、E组第2天开始出现腹泻,第3天全部出现腹泻,其中B、E组腹泻严重。A组肠壁无充血水肿,B、C、D、E组肠壁充血水肿变薄,其中B、E组最重。A组无死亡,C、D组各死亡3只,E组死亡4只,B组死亡6只。B、C、D、E组肠黏膜绒毛变短,肠隐窝变浅,与A组比较差异有统计学意义(P<0.05);C、D组与B组比较差异有统计学意义(P<0.05);B、E组间差异无统计学意义(P>0.05)。结论HD-MTX可致大鼠严重肠黏膜损伤,适宜时间CF解救可减轻HD-MTX对大鼠肠黏膜的损伤,但不能完全阻止其损伤。

Objective To study calcium 5-formyltetrahydrofolate （ CF ） for protecting enteral mucosa after chemotherapy of high-dose methotrexate （ HD-MTX）in different time in rats. Methods Six-week-old Wistar rats were divided into 5 groups. Group A ： control group ; Group B to E. After HD-MTX intraperit neal injection, observed diarrhea and death of rats;CF wasn t injected in guoup B ,and were intramuscular injected in group C to E after 12,24,30 hours respectively. Morphous of jejunum dissection was observed and length of intestinal villus and depth of crypt were measured in section. Results There was no diarrhea in group A. In group B,C,D,E,it began diarrhea on the 2nd day,all appear diarrhea in the 3rd day,groups B,E are most serious. Jejunum walls were congestive,swollen and thin in group B,C,D,E,groups B, E are most serious. Three died in group C and D,4 died in group E,and 6 died in group B. Length of intestinal villus and depth of crypt were reduced in group B to E. These were the most obvious in group E and B was secondary. Significant difference in effect existed between group B,C,D,E and A（ P 〈0. 051 ,the same between group C,D and B,E. There＇s no difference between group C and D （ P 〉 0. 05 ）. Conclusion HD-MTX can cause damage to enteral mucosa in rats; CF can reduce this damage; but cant completely prevent the damage.