黄芩汤预防伊立替康所致迟发性腹泻的研究

目的:探讨中药复方黄芩汤对伊立替康(CPT-11)所致小鼠迟发型腹泻的预防作用.方法:健康雄性ICR小鼠40只随机分为5组,腹泻组ip伊立替康连续5d制备迟发性腹泻模型,正常组等量生理盐水代替,黄芩汤低(5 g·kg-1)、中(10 g·kg-1)、高(20 g·kg-1)剂量组ip伊立替康前1d分别按剂量ig给药,连续用药8d,观察迟发性腹泻发生情况及体重变化；实验第9天将小鼠处死,取血、结肠、盲肠、空肠、回肠组织.光镜下根据Chiu肠黏膜损伤评分方法对肠组织进行分级；Griess法检测肠组织匀浆液一氧化氮(NO)含量；免疫组化法测定增殖细胞核抗原(PCNA)表达水平；瑞士-吉姆萨染色法测定中性粒细胞数.结果:小鼠腹腔注射CPT-11后,出现明显的迟发性腹泻.黄芩汤中、高剂量组小鼠腹泻发生率较腹泻组显著降低(P＜0.05)；体重下降率较腹泻模型组降低；肠黏膜损伤程度比腹泻模型组显著降低,盲肠及结肠的中、高剂量组损伤较腹泻组显著且降低(P＜0.05),与剂量呈一定的量效关系；结肠的NO表达含量明显增加且PCNA表达减少(P＜0.05)；还可增加血中性粒细胞数量(P＜0.01).结论:黄芩汤通过改善肠黏膜损伤程度、增加肠组织NO含量和减少PCNA表达,从而对CPT-11所致迟发性腹泻具有预防作用,还可缓解中性粒细胞减少症.

Experimental Study on Preventive Effect of Huangqin Tang on Irinotecan Induced Delayed Diarrhea

Objective: To observe the prevention effect of Huangqin Tang (HQT) on iriontecan (CPT-11) induced delayed diarrhea in mice. Method: Forty healthy male ICR mice were randomly divided into 5 groups, a model of delayed-onset diarrhea was set up by intraperitoneal injection CPT-11 continuously to establish a model group, control group was given saline instead of irinotecan. Low dosage group (5 g·kg^-1), medium dosage group (10 g·kg^-1) and high dosage group(20 g·kg^-1)of Huangqin Tang were ig administration respectively, once a day for 8 days before one day of ip. The occurrence of delayed diarrhea and the change of body weight were observed;the mice were killed on day 9th, the samples of blood; colon; cecum; jejunum and ileum were collected.The level of mucositis was observed by using light microscope based on Chiu criteria; nitrogen oxide(NO) levels in intestinal tissue homogenate were detected by classic Griess method. The expressions of proliferating cell nuclear antigen(PCNA) were detected by immunohistochemistry. Numbers of neutrophils were determined by Giemsa staining. Result: Injection of CPT-11 could cause significantly delayed diarrhea. The degree of diarrhea incidence from medium and high dosage groups of HQT was significantly lower compared with the diarrhea model group (P<0.05), and the degree of weight loss also got the same result. The degree of intestinal bowel damages resulted from group of cecum; colon's medium and high group of HQT were significantly lower than the diarrhea model group(P<0.05),which showed a certain dose-effect relationship with the dosage. The level of NO expression in colon homogenates was promoted and the PCNA expression in colon mucosa was decreased(P<0.05), the number of neutrophils also got increased (P<0.01). Conclusion: The pre-application HQT can prevent the occurrence of delayed diarrhea CPT-11 by improving the degree of intestinal mucosa, promoting the level of NO expression, decreasing PCNA expression, it can also alleviate neutropenia syndrome.