大剂量甲氨蝶呤化疗对急性淋巴细胞白血病患儿肠粘膜屏障功能影响的研究
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摘要
目的：探讨急性淋巴细胞白血病(ALL)患儿行大剂量甲氨蝶呤(HDMTX)化疗时肠粘膜屏障功能的变化以及和MTX血药浓度的关系。
方法：选取行HDMTX化疗的ALL患儿30例,并分别于化疗开始后1h、24h、44h、68h收集其血液标本；收集正常健康儿童30例血液标本；分离出血浆,采用分光光度法测定内毒素水平和二胺氧化酶(DAO)活性,采取荧光偏振免疫测定法测定血MTX浓度。
结果：ALL患儿行HDMTX化疗开始后1h、24h、44h、68h血浆内毒素及DAO测定结果和对照组比较均有升高,差异有统计学意义(P<0.01)；化疗开始后24h和44血浆内毒素、DAO测定结果较化疗开始后1h有明显升高,以化疗开始后24h最高,差异有统计学意义(P<0.01),化疗开始后1h和68h血浆内毒素、DAO测定结果差别无统计学意义(P>0.05)；在整个化疗过程中,第1次、第2次、第3次和第4次HDMTX化疗相同4个时间位点的血浆内毒素和DAO测定结果比较差异无统计学意义(P>0.05)；化疗开始后监测MTX血药浓度,和血浆内毒素、DAO测定结果测定结果均无相关性(P>0.05)；不同性别、不同年龄组、不同MTX剂量之间,血浆内毒素和DAO测定结果差异无统计学意义(P>0.01)。
结论：ALL患儿在HDMTX化疗过程中,有明显肠粘膜屏障的损伤,以化疗开始后24h最为明显。在化疗结束时,肠粘膜屏障损伤可恢复至化疗开始水平。多次返院HDMTX化疗的ALL患儿,其肠粘膜屏障损伤变化规律类似。ALL患儿和健康儿童比较肠粘膜屏障有明显损伤,可能与长期化疗和疾病本身有关。在HDMTX化疗开始之前ALL患儿是否已经存在肠粘膜屏障的损伤且随着化疗的进行是否有累积加重,以及肠粘膜屏障的损伤和MTX血药浓度的关系仍有待进一步研究。
Objective:To investigate the effects of high-dose methotrexate(HDMTX) treatment on intestinal mucosal barrier in children with acute lymphocytic leukemia(ALL), and the relationship between the plasma concentration of methotrexate and intestinal mucosal barrier dysfunction.
Methods:The blood samples were collected from30children with ALL after1h,24h,44h and68h of intravenous drip(IV drip) HDMTX. At the same time, the blood samples were collected from30normal children. In isolated plasma, the levels of diamine oxidase(DAO) and endotoxin were measured with spectrophotometrie. and the plasma concentration of methotrexate were determined with fluorescence polarization immunoassay.
Results:The level of plasma endotoxin and DAO after1h,24h,44h,68h of IV drip HDMTX were respectively higher in ALL group than in normal control group, the difference was statistically significant(P<0.01). The level of plasma endotoxin and DAO were both higher after24h and44h of IV drip HDMTX than after1h and68h of IV drip HDMTX, and reach the peak at24h. the difference was statistically significant(P<0.01). There was no significant difference between the measured results of plasma endotoxin and DAO after1h and68h of IV drip HDMTX(P>0.05). During the different courses of HDMTX treament in same patients, there was no significant difference about the levels of endotoxin and DAO between the different courses(P>0.05). The plasma concentration of methotrexate monitored was no significantly related to the level of plasma endotoxin and DAO after1h,24h,44h.68h of IV drip HDMTX(P>0.05). There were no significant difference between the male group and female group,3g/m2group and5g/m2group,3～7years old group and7-12years old group (P>0.05).
Conclusions:HDMTX treatment has great effects on intestinal mucosal barrier in children with ALL, the damage is the most serious after24h of IV drip HDMTX. In the end of chemotherapy, the damage can be recovered to level of beginning chemotherapy. During the different courses of HDMTX in same patients, the intestinal mucosa barrier damage change rules are similar. Compared to the normal control group, there was obvious damage in the ALL group, which maybe correlate to the disease itself or the long-term chemotherapy. It still needs further research and understands whether there has been intestinal mucosa barrier injury before HDMTX treatment in ALL children and whether there is a cumulative increased damage in intestinal mucosa barrier.
方法：选取行HDMTX化疗的ALL患儿30例,并分别于化疗开始后1h、24h、44h、68h收集其血液标本；收集正常健康儿童30例血液标本；分离出血浆,采用分光光度法测定内毒素水平和二胺氧化酶(DAO)活性,采取荧光偏振免疫测定法测定血MTX浓度。
结果：ALL患儿行HDMTX化疗开始后1h、24h、44h、68h血浆内毒素及DAO测定结果和对照组比较均有升高,差异有统计学意义(P<0.01)；化疗开始后24h和44血浆内毒素、DAO测定结果较化疗开始后1h有明显升高,以化疗开始后24h最高,差异有统计学意义(P<0.01),化疗开始后1h和68h血浆内毒素、DAO测定结果差别无统计学意义(P>0.05)；在整个化疗过程中,第1次、第2次、第3次和第4次HDMTX化疗相同4个时间位点的血浆内毒素和DAO测定结果比较差异无统计学意义(P>0.05)；化疗开始后监测MTX血药浓度,和血浆内毒素、DAO测定结果测定结果均无相关性(P>0.05)；不同性别、不同年龄组、不同MTX剂量之间,血浆内毒素和DAO测定结果差异无统计学意义(P>0.01)。
结论：ALL患儿在HDMTX化疗过程中,有明显肠粘膜屏障的损伤,以化疗开始后24h最为明显。在化疗结束时,肠粘膜屏障损伤可恢复至化疗开始水平。多次返院HDMTX化疗的ALL患儿,其肠粘膜屏障损伤变化规律类似。ALL患儿和健康儿童比较肠粘膜屏障有明显损伤,可能与长期化疗和疾病本身有关。在HDMTX化疗开始之前ALL患儿是否已经存在肠粘膜屏障的损伤且随着化疗的进行是否有累积加重,以及肠粘膜屏障的损伤和MTX血药浓度的关系仍有待进一步研究。
Objective:To investigate the effects of high-dose methotrexate(HDMTX) treatment on intestinal mucosal barrier in children with acute lymphocytic leukemia(ALL), and the relationship between the plasma concentration of methotrexate and intestinal mucosal barrier dysfunction.
Methods:The blood samples were collected from30children with ALL after1h,24h,44h and68h of intravenous drip(IV drip) HDMTX. At the same time, the blood samples were collected from30normal children. In isolated plasma, the levels of diamine oxidase(DAO) and endotoxin were measured with spectrophotometrie. and the plasma concentration of methotrexate were determined with fluorescence polarization immunoassay.
Results:The level of plasma endotoxin and DAO after1h,24h,44h,68h of IV drip HDMTX were respectively higher in ALL group than in normal control group, the difference was statistically significant(P<0.01). The level of plasma endotoxin and DAO were both higher after24h and44h of IV drip HDMTX than after1h and68h of IV drip HDMTX, and reach the peak at24h. the difference was statistically significant(P<0.01). There was no significant difference between the measured results of plasma endotoxin and DAO after1h and68h of IV drip HDMTX(P>0.05). During the different courses of HDMTX treament in same patients, there was no significant difference about the levels of endotoxin and DAO between the different courses(P>0.05). The plasma concentration of methotrexate monitored was no significantly related to the level of plasma endotoxin and DAO after1h,24h,44h.68h of IV drip HDMTX(P>0.05). There were no significant difference between the male group and female group,3g/m2group and5g/m2group,3～7years old group and7-12years old group (P>0.05).
Conclusions:HDMTX treatment has great effects on intestinal mucosal barrier in children with ALL, the damage is the most serious after24h of IV drip HDMTX. In the end of chemotherapy, the damage can be recovered to level of beginning chemotherapy. During the different courses of HDMTX in same patients, the intestinal mucosa barrier damage change rules are similar. Compared to the normal control group, there was obvious damage in the ALL group, which maybe correlate to the disease itself or the long-term chemotherapy. It still needs further research and understands whether there has been intestinal mucosa barrier injury before HDMTX treatment in ALL children and whether there is a cumulative increased damage in intestinal mucosa barrier.
引文
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