唐草片对伊立替康所致小鼠毒性的保护作用
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摘要
目的观察治疗艾滋病中药唐草片对伊立替康引起的小鼠毒性的防治作用。方法健康昆明小鼠腹腔注射盐酸伊立替康20mg/kg,每天1次,连续6天,制备迟发型腹泻动物模型,唐草片连续灌胃给药16天。结果注射伊立替康后第7天,动物体重下降幅度最大,为11.8%。而预防性给予唐草片的小鼠,体重下降4.3%,明显小于伊立替康组(P<0.05)。给予唐草片组动物白细胞数为(2.11±0.99)×10~9/L,显著高于伊立替康组(1.26±0.46)×10~9/L(P<0.05)。唐草片组小鼠迟发性腹泻发生时间比伊立替康组推迟2天,腹泻发生率4.91%,低于伊立替康组腹泻发生率52.5%(P<0.05)。小肠组织标本固定后进行HE染色,伊立替康组黏膜部分绒毛顶端断裂破损,上皮细胞肿胀、变性、坏死,炎性细胞大量浸润,正常腺体减少;唐草片治疗组黏膜组织基本正常,少量炎症细胞浸润。结论唐草片可以减轻伊立替康引起的肠黏膜损伤、延缓迟发型腹泻。
Objective To observe the preventive and therapeutic effects of Tangcaopian on toxicity of irinotecan in mice. Methods A delayed diarrhea animal model was established by intraperitoneal injection of irinotecan hydrochloride 20 mg/kg once a day for 6 consecutive days in healthy Kunming mice. Tangcaopian was orally administered for 16 consecutive days. Results On the seventh day after first injection of irinotecan, the maximum body weight decreased by 11.8%. However, the weight loss of mice treated with Tangcaopian preventive treatment was 4.3%, significantly lower than that of the irinotecan group(P<0.05). The number of white blood cells in Tangcaopian group was(2.11 ±0.99) ×10~9/L, significantly higher than that in irinotecan group(1.26 ±0.46) ×10~9/L(P<0.05). The occurrence time of delayed diarrhea in mice treated with Tangcaopian was 2 days later than that in the irinotecan group. The total incidence of diarrhea was 4.91% in Tangcaopian group, 52.5% lower than that in irinotecan group(P<0.05). The specimens of small intestinal tissue were stained with H.E. The top of the villus in intestinal mucosa of irinotecan group was damaged, and the epithelial cells were swollen, denatured, necrotic, inflammatory cells infiltrated and normal glands decreased. The mucosal tissue of the Tangcaopian group was almost normal and a small amount of inflammatory cells infiltrated. Conclusion Tangcaopian can alleviate irinotecan induced intestinal mucosal injury and prevent delayed diarrhea.
Objective To observe the preventive and therapeutic effects of Tangcaopian on toxicity of irinotecan in mice. Methods A delayed diarrhea animal model was established by intraperitoneal injection of irinotecan hydrochloride 20 mg/kg once a day for 6 consecutive days in healthy Kunming mice. Tangcaopian was orally administered for 16 consecutive days. Results On the seventh day after first injection of irinotecan, the maximum body weight decreased by 11.8%. However, the weight loss of mice treated with Tangcaopian preventive treatment was 4.3%, significantly lower than that of the irinotecan group(P<0.05). The number of white blood cells in Tangcaopian group was(2.11 ±0.99) ×10~9/L, significantly higher than that in irinotecan group(1.26 ±0.46) ×10~9/L(P<0.05). The occurrence time of delayed diarrhea in mice treated with Tangcaopian was 2 days later than that in the irinotecan group. The total incidence of diarrhea was 4.91% in Tangcaopian group, 52.5% lower than that in irinotecan group(P<0.05). The specimens of small intestinal tissue were stained with H.E. The top of the villus in intestinal mucosa of irinotecan group was damaged, and the epithelial cells were swollen, denatured, necrotic, inflammatory cells infiltrated and normal glands decreased. The mucosal tissue of the Tangcaopian group was almost normal and a small amount of inflammatory cells infiltrated. Conclusion Tangcaopian can alleviate irinotecan induced intestinal mucosal injury and prevent delayed diarrhea.
引文
[1] Fujita K,Kubota Y,Ishida H,et al.Irinotecan,a key chemotherapeutic drug for metastatic colorectal cancer[J].World J Gastroenterol,2015,21(43):12234-12248.
[2] Stein A,Voigt W,Jordan K.Chemotherapy-induced diarrhea:pathophysiology,frequency and guideline-based management[J].Ther Adv Med Oncol,2010,2(1):51-63.
[3] 中国中医药信息杂志社.中成药“唐草片”获得批准用于改善艾滋病症状[J].中国中医药信息杂志,2004,11 (5):466.
[4] 邵宝平,杨莉娅,李倩,等.艾滋病辅助治疗药——唐草片上市10年运用回顾[J].中国艾滋病性病,2017,23(10):978-979.
[5] 陈军,张仁芳,王江蓉,等.HAART联合中成药唐草片治疗HIV感染的有效性及安全性研究[J].上海医药,2014,35(21):17-19.
[6] 殷建华,吴剑,杨克宗,等.抗艾滋病中成药唐草片抗氧化性的研究[J].中国现代中药,2009,11(12):38-40.
[7] 吴鑫磊,郭玉忠,范磊,等.唐草片对注射氢化可的松小鼠的免疫保护作用[J].中国医院药学杂志,2013,33(23):1931-1934.
[8] Kurita A,Kado S,Kaneda N,et al.Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats[J].Cancer Chemother Pharmacol,2004,46(3):211-220.
[9] Kurita A,Kado S,Matsumoto T,et al.Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of beta-glucuronidase activity in intestinal lumen[J].Cancer Chemother Pharmacol,2011,67(1):201-213.
[10] Ramesh M,Ahlawat P,Srinivas NR.et al.Irinotecan and its active metabolite,SN-38:review of bioanalytical methods and recent update from clinical pharmacology perspectives[J].Biomed Chromatogr,2010,24(1):104-123.
[11] Cinausero M,Aprile G,Ermacora P,et al.New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury[J].Front Pharmacol,2017,8(354):1-12.
[12] Mego M,Chovanec J,Vochyanova-Andrezalova I,et al.Prevention of irinotecan induced diarrhea by probiotics:A randomized double blind,placebo controlled pilot study[J].Complement Ther Med,2015,23(3):356-362.
[13] 杨莉娅,邵宝平,李倩,等.唐草片的临床研究与应用[J].中国中医药现代远程教育,2015,12(4):14-17.
[14] 郭玉忠,海莉丽,乔政维,等.唐草片对注射丝裂霉素C小鼠造血功能的保护作用[J].中华实用诊断与治疗杂志,2016,30(12):1184-1186.
[2] Stein A,Voigt W,Jordan K.Chemotherapy-induced diarrhea:pathophysiology,frequency and guideline-based management[J].Ther Adv Med Oncol,2010,2(1):51-63.
[3] 中国中医药信息杂志社.中成药“唐草片”获得批准用于改善艾滋病症状[J].中国中医药信息杂志,2004,11 (5):466.
[4] 邵宝平,杨莉娅,李倩,等.艾滋病辅助治疗药——唐草片上市10年运用回顾[J].中国艾滋病性病,2017,23(10):978-979.
[5] 陈军,张仁芳,王江蓉,等.HAART联合中成药唐草片治疗HIV感染的有效性及安全性研究[J].上海医药,2014,35(21):17-19.
[6] 殷建华,吴剑,杨克宗,等.抗艾滋病中成药唐草片抗氧化性的研究[J].中国现代中药,2009,11(12):38-40.
[7] 吴鑫磊,郭玉忠,范磊,等.唐草片对注射氢化可的松小鼠的免疫保护作用[J].中国医院药学杂志,2013,33(23):1931-1934.
[8] Kurita A,Kado S,Kaneda N,et al.Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats[J].Cancer Chemother Pharmacol,2004,46(3):211-220.
[9] Kurita A,Kado S,Matsumoto T,et al.Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of beta-glucuronidase activity in intestinal lumen[J].Cancer Chemother Pharmacol,2011,67(1):201-213.
[10] Ramesh M,Ahlawat P,Srinivas NR.et al.Irinotecan and its active metabolite,SN-38:review of bioanalytical methods and recent update from clinical pharmacology perspectives[J].Biomed Chromatogr,2010,24(1):104-123.
[11] Cinausero M,Aprile G,Ermacora P,et al.New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury[J].Front Pharmacol,2017,8(354):1-12.
[12] Mego M,Chovanec J,Vochyanova-Andrezalova I,et al.Prevention of irinotecan induced diarrhea by probiotics:A randomized double blind,placebo controlled pilot study[J].Complement Ther Med,2015,23(3):356-362.
[13] 杨莉娅,邵宝平,李倩,等.唐草片的临床研究与应用[J].中国中医药现代远程教育,2015,12(4):14-17.
[14] 郭玉忠,海莉丽,乔政维,等.唐草片对注射丝裂霉素C小鼠造血功能的保护作用[J].中华实用诊断与治疗杂志,2016,30(12):1184-1186.