对赛北紫堇总生物碱的急性、亚慢性经口毒性试验研究  

Experimental Study on Acute and Sub-chronic Oral Toxicity of Total Alkaloids from Corydalis Impatiens

作　　者：李珂 华玉美多 杨占婷[2] 张得钧 李占强[2] 樊海宁[3] 芦殿香[2] LI Ke;HUAYU Meiduo;YANG Zhanting;ZHANG Dejun;LI Zhanqiang;FAN Haining;LU Dianxiang(School of Ecological and Environmental Engineering,Qinghai university,Xining,810001;Research Center for High Altitude Medicine,Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province(Qinghai-Utah Joint Research Key Lab for High Altitude Medicine),Qinghai University,Xining 810001;Department of Hepatopancreatobiliary Surgery,Key Laboratory for Hydatid Diseases of Qinghai Province,Affiliated Hospital of Qinghai University,Xining 810001)

机构地区：[1]青海大学生态环境工程学院,青海西宁810001 [2]青海大学高原医学研究中心,青海省高原医学应用基础重点实验室,青海-犹他高原医学联合重点实验室,青海西宁810001 [3]青海大学附属医院肝胆胰外科,青海省包虫病重点实验室,青海西宁810001

出　　处：《中国高原医学与生物学杂志》2019年第4期260-267,共8页Journal of Chinese High Altitude Medicine & Biology

基　　金：青海省科技厅重大专项(2016-SF-A5)

摘　　要：目的评价赛北紫堇总生物碱对小鼠的急性、亚慢性经口毒性。方法总生物碱用85%乙醇提取,酸化除杂、碱化沉淀获得赛北紫堇总生物碱。利用寇氏法测定赛北紫堇总生物碱的LD50。将昆明小鼠分为4组:空白组、低剂量组(5.0mg/kg)、中剂量组(10.0mg/kg)、高剂量组(20.0mg/kg),每组12只,雌雄各半,对小鼠进行28 d的亚慢性经口毒性研究。末次给药后,禁食12 h,自由饮水。经眼球取血,利用半自动血液分析仪进行全血分析。利用生化试剂盒测定血清AST、ALT、GRE、BUN、TG、T-CHO、ALB含量。取小鼠的心、肝、脾、肺、肾,计算脏器指数,并用HE染色法观察赛北紫堇总生物碱对组织形态学的影响。结果赛北紫堇总生物碱口服时的LD50为42.9 mg/kg。亚慢性毒性研究发现,给药组雌鼠体重低于雄鼠。雌鼠心脏指数明显低于空白组;雄鼠低、高剂量组的肺指数与空白组相比明显降低。与空白组相比药物组雌鼠WBC、Mon、Neu、Eas、Lym、RBC、HGB、HCT、RDW-CV、RDW-SD升高,P<0.05;雄鼠的Neu、Bas、RBC、HGB、HCT、RDW-CV、RDW-SD、PLT与空白组相比明显升高。雌鼠中、高剂量组的ALT、BUN、TG均高于空白剂量组(P<0.05);雄鼠低、中剂量组的ALT,低、高剂量组的AST小于空白剂量组;雄鼠3个剂量组的ALB均比空白组高;雄鼠高剂量组的CRE高于空白组。雌鼠空白、低、中、高剂量组的AST、BUN高于雄鼠。雌鼠药物组的ALB低于雄鼠,AST、BUN高于雄鼠;雌鼠高剂量组的TG高于雄鼠。组织病理切片显示,小鼠肺组织支气管产生炎性浸润;肝组织产生炎症浸润,肝细胞核萎缩,肝索结构模糊,局部水肿;肾脏出现凝固性坏死。结论急性小鼠出现中毒表现;亚慢性小鼠肝、肾损伤严重,且雌鼠损伤大于雄鼠。Objective To evaluate the acute and subchronic toxicity of total alkaloids from Corydalis impatiens.Methods The total alkaloids were extracted with 85%ethanol,acidified to remove impurities,and alkalized to obtain total alkaloids of C.impatiens.The LD50 of total alkaloids from C.impatiens was determined by the method of Korbor.Kunming mice were divided into 4 groups:blank group,low dose group(5.0 mg/kg),middle dose group(10.0 mg/kg),high dose group(20.0 mg/kg),with 12 mice in each group,half male and half female.The mice were subjected to a 28-day sub-chronic oral toxicity study.After the last drug,all groups stop feeding about 12 hours,free to drink water.Blood was taken from the eyeball and whole blood analysis was performed using a semi-automatic blood analyzer.The serum levels of AST,ALT,GRE,BUN,TG,T-CHO and ALB were determined by biochemical indicators.The heart,liver,spleen,lung and kidney of the mice were taken,the organ index was calculated,and the effect of total alkaloids of C.impatiens on histomorphology was observed by HE staining.Results The LD50 of the C.impatiens total alkaloids was 42.9 mg/kg.Sub-chronic toxicity studies found that female mice in the drug group weighed less than male mice.The heart index of female mice was significantly lower than the blank group;the lung index of the low and high dose groups of male mice was significantly lower than the blank group.Compared with the blank group,the WBC,Mon,Neu,Eas,Lym,RBC,HGB,HCT,RDW-CV,and RDW-SD of the female group were increased(P<0.05).Neu,Bas,RBC,HGB,of the male mice.HCT,RDW-CV,RDW-SD,and PLT were significantly higher than those in the blank group.The ALT,BUN and TG in the middle and high dose groups of female mice were higher than those in blank group(P<0.05).The AST and BUN of the female group and the low,medium and high dose groups were higher than those in male mice.The ALB of the female group was lower than that in male mice,and the AST and BUN were higher than those in the male mice.The high dose of the female mice TG was higher than m

关 键 词：赛北紫堇 总生物碱 小鼠 急性 亚慢性 毒性 

分 类 号：R965.3[医药卫生—药理学]