三七总皂苷亚慢性毒性试验研究
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摘要
[目的]评价三七总皂苷(PNS)用药安全性,为临床用药提供参考依据。[方法]将40只昆明系小白鼠随机分为4组,每组10只,3个药物处理组小鼠通过腹腔注射的方式分别给予11.34、56.70、113.40mg/(kg·BW)的PNS,每天1次,连续给药14 d;空白对照组小鼠腹腔注射生理盐水0.3 mL/只,连续注射14 d。测定并比较各组小鼠在试验期间的体重、脏器指数(肝脏、脾脏、肾脏指数)以及血液生化指标;取各组小鼠肝脏、脾脏、肾脏组织,制备病理组织切片,利用显微镜观察上述组织是否出现病理变化。[结果]3个PNS给药组小鼠在试验期间的体重与空白对照组小鼠相比,均无显著性差异(P>0.05);11.34 mg/(kg·BW)PNS组小鼠的脾脏指数显著低于空白对照组(P<0.05);113.40 mg/(kg·BW)PNS组小鼠的谷草转氨酶活力和肌酐含量显著低于空白对照组(P<0.05),而尿素氮含量显著升高(P<0.05);病理组织学观察结果表明,PNS对肝脏、脾脏、肾脏组织无明显损伤。[结论]PNS实际无毒,长期用药会产生肾毒性,提示用药不宜过量。
[Objective] To evaluate the safety of Panax notoginseng saponins(PNS) for clinical use. [Method] A total of 40 Kunming mice were randomly divided into four groups with 10 mice in each group. Mice in the three experimental groups were intraperitoneally injected with 11.34, 56.70, 113.40 mg/(kg·BW) PNS once a day for 14 consecutive days; mice in the blank control group were intraperitoneally injected with 0.3 mL of normal saline for 14 consecutive days. The body weight, organ index(liver, spleen and kidney index) and blood biochemical indexes of mice in each group were measured and compared; the liver,spleen and kidney tissues of mice in each group were taken to prepare histopathological slide, and the pathological changes of the above tissues were observed by microscopy. [Result] There was no significant difference in body weight between the three PNS treatment groups and the blank control group(P>0.05); the spleen index of 11.34 mg/(kg·BW) PNS group was significantly lower than that of the blank control group(P <0.05); the aspartate aminotransferase activity and serum creatinine content of113.40 mg/(kg·BW) PNS group were significantly lower than that of the blank control group(P<0.05), while blood urea nitrogen content was significantly higher than that of the blank control group(P<0.05); the histopathological observation demonstrated that PNS had no obvious damage to liver, spleen and kidney. [Conclusion] PNS is actually non-toxic, but its long-term use can produce nephrotoxicity, suggesting that the clinical use of PNS should not be excessive.
[Objective] To evaluate the safety of Panax notoginseng saponins(PNS) for clinical use. [Method] A total of 40 Kunming mice were randomly divided into four groups with 10 mice in each group. Mice in the three experimental groups were intraperitoneally injected with 11.34, 56.70, 113.40 mg/(kg·BW) PNS once a day for 14 consecutive days; mice in the blank control group were intraperitoneally injected with 0.3 mL of normal saline for 14 consecutive days. The body weight, organ index(liver, spleen and kidney index) and blood biochemical indexes of mice in each group were measured and compared; the liver,spleen and kidney tissues of mice in each group were taken to prepare histopathological slide, and the pathological changes of the above tissues were observed by microscopy. [Result] There was no significant difference in body weight between the three PNS treatment groups and the blank control group(P>0.05); the spleen index of 11.34 mg/(kg·BW) PNS group was significantly lower than that of the blank control group(P <0.05); the aspartate aminotransferase activity and serum creatinine content of113.40 mg/(kg·BW) PNS group were significantly lower than that of the blank control group(P<0.05), while blood urea nitrogen content was significantly higher than that of the blank control group(P<0.05); the histopathological observation demonstrated that PNS had no obvious damage to liver, spleen and kidney. [Conclusion] PNS is actually non-toxic, but its long-term use can produce nephrotoxicity, suggesting that the clinical use of PNS should not be excessive.
引文
[1]国家药典委员会.中华人民共和国药典[M].2015年版.北京:中国医药科技出版社,2015.
[2]张元杰,周兰,来国防,等.整体柱HPLC法测定三七总皂苷中的5种皂苷成分[J].中国药师,2017,20(10):1879-1881.
[3]陈红艳,陈安,卢芳国,等.三七总皂苷的药理研究进展[J].湖南中医杂志,2019,35(1):154-157.
[4]SUN H X,XIE Y,YE Y P.Advances in saponin-based adjuvants[J].Vaccine,2009,27(12):1787-1796.
[5]马涛,辛文锋,张文生,等.三七皂苷R1对Aβ1-42诱导的SH-SY5Y细胞凋亡的保护作用[J].中国中药杂志,2015,40(2):303-307.
[6]梁丽英,陈晶,陈朝.三七总皂苷通过调节Caspase-3、Caspase-9的表达诱导肝癌细胞BEL-7404凋亡的研究[J].右江医学,2018,46(6):623-627.
[7]李淑慧,李晓辉,楚延,等.三七总皂苷抗炎作用机制的实验研究[J].中草药,2000,31(9):676-678.
[8]江源,刘翠,陈清彬,等.三七皂苷Rg1对小鼠免疫功能的影响[J].中国现代中药,2006,8(3):9-11.
[9]洪梅,孙文静,毕昱.三七总皂苷对免疫性肝损伤小鼠的保护作用[J].实用临床医药杂志,2011(1):9-14.
[10]郭时金,徐倩倩,付石军,等.清瘟败毒颗粒的急性和亚慢性毒性试验研究[J].家畜生态学报,2014,35(1):61-64.
[11]农业农村部兽药评审中心.兽药研究技术指导原则汇编[G].北京:化学工业出版社,2012.
[12]马玉奎,戴晓莉.三七总皂苷安全性的实验研究[J].食品与药品,2011,13(6):408-411.
[13]LIU Z G,XING J,ZHENG S S,et al.Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response[J].Carbohydrate Polymers,2016(142):141-148.
[14]BOGIN E,PEH H C,AVIDAR Y,et al.Sex and genotype dependence on the effects of long-term high environmental temperatures on cellular enzyme activities from chicken organs[J].Avian Pathology,1997,26(3):511-524.
[15]ZHU M,LIN K F,YEUNG R Y,et al.Evaluation of the protective effects of Schisandra chinensis on PhaseⅠdrug metabolism using a CCl4intoxication model[J].Journal of Ethnopharmacology,1999,67(1):61-68.
[16]唐娇,赵敏,谭剑斌,等.三七的经口急性毒性及亚慢性毒性研究[J].华南预防医学,2015(6):521-526.
[17]DEPIERREUX M,DAMME B V,HOUTE K V,et al.Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs[J].American Journal of Kidney Diseases,1994,24(2):172-180.
[18]陈成伟.药物与中毒性肝病[M].上海:上海科学技术出版社,2002:74.
[19]武强,王龙武,申春梅.肌氨酸氧化酶法测定健康成人血清肌酐参考值的建立[J].检验医学,2009,24(1):69-70.
[20]董书清.血清肌酐、尿素氮的检测值及其比值与肾脏损害的探讨[J].中国医药指南,2011,9(36):136-137.
[21]韩刚,孙辉业,董延生,等.三七总皂苷对大鼠肝脏肾脏的毒性作用[J].中国新药杂志,2006,15(24):2115-2118.
[2]张元杰,周兰,来国防,等.整体柱HPLC法测定三七总皂苷中的5种皂苷成分[J].中国药师,2017,20(10):1879-1881.
[3]陈红艳,陈安,卢芳国,等.三七总皂苷的药理研究进展[J].湖南中医杂志,2019,35(1):154-157.
[4]SUN H X,XIE Y,YE Y P.Advances in saponin-based adjuvants[J].Vaccine,2009,27(12):1787-1796.
[5]马涛,辛文锋,张文生,等.三七皂苷R1对Aβ1-42诱导的SH-SY5Y细胞凋亡的保护作用[J].中国中药杂志,2015,40(2):303-307.
[6]梁丽英,陈晶,陈朝.三七总皂苷通过调节Caspase-3、Caspase-9的表达诱导肝癌细胞BEL-7404凋亡的研究[J].右江医学,2018,46(6):623-627.
[7]李淑慧,李晓辉,楚延,等.三七总皂苷抗炎作用机制的实验研究[J].中草药,2000,31(9):676-678.
[8]江源,刘翠,陈清彬,等.三七皂苷Rg1对小鼠免疫功能的影响[J].中国现代中药,2006,8(3):9-11.
[9]洪梅,孙文静,毕昱.三七总皂苷对免疫性肝损伤小鼠的保护作用[J].实用临床医药杂志,2011(1):9-14.
[10]郭时金,徐倩倩,付石军,等.清瘟败毒颗粒的急性和亚慢性毒性试验研究[J].家畜生态学报,2014,35(1):61-64.
[11]农业农村部兽药评审中心.兽药研究技术指导原则汇编[G].北京:化学工业出版社,2012.
[12]马玉奎,戴晓莉.三七总皂苷安全性的实验研究[J].食品与药品,2011,13(6):408-411.
[13]LIU Z G,XING J,ZHENG S S,et al.Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response[J].Carbohydrate Polymers,2016(142):141-148.
[14]BOGIN E,PEH H C,AVIDAR Y,et al.Sex and genotype dependence on the effects of long-term high environmental temperatures on cellular enzyme activities from chicken organs[J].Avian Pathology,1997,26(3):511-524.
[15]ZHU M,LIN K F,YEUNG R Y,et al.Evaluation of the protective effects of Schisandra chinensis on PhaseⅠdrug metabolism using a CCl4intoxication model[J].Journal of Ethnopharmacology,1999,67(1):61-68.
[16]唐娇,赵敏,谭剑斌,等.三七的经口急性毒性及亚慢性毒性研究[J].华南预防医学,2015(6):521-526.
[17]DEPIERREUX M,DAMME B V,HOUTE K V,et al.Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs[J].American Journal of Kidney Diseases,1994,24(2):172-180.
[18]陈成伟.药物与中毒性肝病[M].上海:上海科学技术出版社,2002:74.
[19]武强,王龙武,申春梅.肌氨酸氧化酶法测定健康成人血清肌酐参考值的建立[J].检验医学,2009,24(1):69-70.
[20]董书清.血清肌酐、尿素氮的检测值及其比值与肾脏损害的探讨[J].中国医药指南,2011,9(36):136-137.
[21]韩刚,孙辉业,董延生,等.三七总皂苷对大鼠肝脏肾脏的毒性作用[J].中国新药杂志,2006,15(24):2115-2118.