不同剂量四氢叶酸钙对大剂量甲氨蝶呤化疗大鼠肠黏膜的保护作用

Different Doses of Calcium 5-Formyltetrahydrofolate for Protecting Enteral Mucosa after Chemotherapy of High-Dose Methotrexate in Rats

目的探讨不同剂量四氢叶酸钙(CF)对大剂量甲氨蝶呤(HD-MTX)化疗大鼠肠黏膜的保护作用。方法6周龄Wistar大鼠60只随机分为5组,每组12只。A组:正常对照组,腹腔注射9g/L盐水;B组:1%CF解救组(即CF解救剂量为MTX总量的1%,下同);C组:2%CF解救组;D组:8%CF解救组;E组:空白对照组,不予CF解救。B～E组均腹腔注射MTX(120mg/kg),B～D组于腹腔注射MTX12h后肌注CF解救,1次/6h,共7次。于最后一次肌注CF18h后杀死大鼠,取其空肠标本观察形态,切片观察测定绒毛长度隐窝深度。结果A组肠壁厚弹性好,绒毛密集、排列整齐;B～E组肠壁充血水肿变薄,小肠绒毛变短,隐窝深度变浅。E组最重,B组次之。B～E组与A组比较有统计学差异(Pa<0.05);C、D与B、E组比较有统计学差异(Pa<0.05);C、D组比较无统计学差异(P>0.05)。结论MTX可致大鼠黏膜损害,CF解救可减轻其黏膜损害,过度降低CF解救剂量达不到解救目的。

Objective To explore different doses of calcium 5 - formyltetrahydrofolate （CF） for protecting enteral mucosa after chemotherapy of high - dose methotrexate（ HD - MTX） in rats. Methods Sixty of 6 weeks old Wistar rats were divided into 5 groups in random, 12 rats every group. Group A： control group,normal sodium（NS） intraperitoneal injection only; Group B to E：after HD- MTX intraperitoneal injection （120 mg/kg）, 1% CF（CF dose amounts to 1% of total MTX dose） for group B, 2% CF for group C, 8% CF for Group D and empty for group E. For group B,C and D, CF were intramuscular injected after 12 hours of MTX used, q6h ×7 times. Rats were killed after 18 hours of the last time of CF. Morphous of jejunum dissection were observed and length of intestinal villus and depth of crypt were measured. Results For group A ,jejunum walls were thick and elastic and intestinal villus were close and orderly. Jejunum walls were congestive,swollen and thin, length of intestinal villus and depth of crypt reduced both in group B to E. These were most obvious in group E,and were secondary in group B. Statistical analysis showed that significant difference in effect existed between group B, C, D,E and group A（ P 〈 0. 05）, same between group C,D and group B, E （ P 〈 0. 05 ）. No difference between group C and D （ P 〉 0.05 ） Conclusion MTX can damage in intestinal mucosa of rats,CF can reduce this damage,excessive low doses of CF can＇t play this role.