毒性剂量下不同产地附子醇提物对急性心衰大鼠的影响  

The effect of Fuzi alcohol extract from different habitats on rats with acute heart failure at toxic dose

作　　者：李静 彭成[1] 熊芳 蒲琳 徐虹 谢晓芳[1] LI Jing;PENG Cheng;XIONG Fang;PU Lin;XU Hong;XIE Xiao-fang(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]西南特色中药资源国家重点实验室,成都中医药大学药学院,四川成都611137

出　　处：《中药与临床》2024年第1期50-57,共8页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金重大项目:中药道地性“性-效”关系研究(NO.81891012),中药道地性研究(NO.81891010);国家自然科学基金区域联合项目:川产道地药材的道地性研究(NO.U19A2010);国家中医药多学科交叉创新团队项目:西南特色中药资源多维评价多学科交叉创新团队(NO.ZYYCXTD-D-202209);四川省中医药科技产业创新团队:特色中药资源多维评价与产品开发创新团队(NO.2022C001)。

摘　　要：目的:比较不同产地附子醇提物在毒性剂量对急性心力衰竭(acute heart failure,AHF)大鼠的影响。方法:通过股静脉注射盐酸普罗帕酮建立急性心力衰竭大鼠模型,经十二指肠给予五个产地附子药材醇提液(四川江油JY、四川布拖BT、云南昆明YN、陕西城固SX、河北安国HB,)7 g·kg^(-1)。采用生理记录仪记录给药60 min心脏血流动力学指标变化,采血测定LDH(乳酸脱氢酶)、CKMB(肌酸激酶同工酶)、Ca^(2+)、BNP(脑尿钠肽)、Ang-Ⅱ(血管紧张素Ⅱ)、ALD(醛固酮)和TNF-α(肿瘤坏死因子-α)的水平,并对主要脏器称量计算脏器系数。结果:与模型组比较,五个产地附子醇提物对大鼠血流动力学参数+LV dp/dtmax、HR均呈现先升高后降低的趋势,给药60 min时均低于模型组大鼠;对-LV dp/dtmax均具有一定的降低后升高的趋势,给药60 min时均高于模型组大鼠;与JY组相比,BT组+LV dp/dtmax在给药后5 min显著升高(P<0.05),SX组+LV dp/dtmax在给药后30 min显著降低(P<0.05);各附子治疗组均可进一步升高模型大鼠血清LDH活性和CKMB、BNP、Ang-Ⅱ、ALD、TNF-α含量,同时降低Ca^(2+)含量(P<0.05或P<0.01)。与JY组相比,BT、SX组BNP含量显著升高(P<0.01),CKMB、LDH水平显著升高(P<0.05或P<0.01),SX组ALD含量显著升高(P<0.05)。与模型组相比,HB、SX组脾、胸腺指数明显降低(P<0.01),JY组肺、肝指数明显降低(P<0.05或P<0.01),BT组肺指数明显降低(P<0.01)。与JY组相比,HB组肝、脾指数明显降低(P<0.05或P<0.01),BT组心脏、肝指数明显升高(P<0.01),SX组脾、胸腺指数明显降低(P<0.05或P<0.01),YN组肝指数明显升高(P<0.01)。结论:在7g·kg^(-1)剂量下,不同产地附子均对急性心衰大鼠有明显毒性,表现为心脏负担加剧、心肌损伤及心肌酶学的进一步加重,同时对脾、胸腺等主要脏器指数有抑制,毒性强度由高到低为:云南昆明>四川布拖>陕西城固>四川江油>河北安国。Objective:The study aimed to compare the toxic effects of Fuzi alcohol extract from different habitats on acute heart failure(AHF)rats.Method:AHF rats were established by femoral vein injection of propafenone hydrochloride.7g·kg^(-1)of Fuzi Alcohol extracts from five origins(Jiangyou Sichuan JY,Butuo Sichuan BT,Kunming Yunnan YN,Chenggu Shaanxi SX and Anguo Hebei HB)were given through duodenum.The changes of cardiac hemodynamic indexes within 60 min of administration were recorded by physiological recorder.Serum was collected to detect the concentrations of lactate dehydrogenase(LDH),levels of creatine phosphokinase isoenzyme(CKMB),Ca^(2+),brain natriuretic peptide(BNP),angiotensin Ⅱ(Ang-Ⅱ),aldosterone(ALD),and tumor necrosis factor-α(TNF-α).The main organs were weighed and the organ coefficients were calculated.Result:Compared with model group,the rats hemodynamic parameters+LV dp/dtmax and HR of Fuzi alcohol extract from five producing areas were firstly increased and then decreased,and were lower than those of model group after 60 min administration.-LV dp/dtmax were firstly decreased and then increased,and were higher than those of model group after 60 min administration.Compared with JY group,+LV dp/dtmax in BT group was significantly increased at 5 min after administration(P<0.05),and+LV dp/dtmax in SX group was significantly decreased at 30 min after administration(P<0.05).The activity of LDH and the contents of CKMB,BNP,Ang-Ⅱ,ALD and TNF-α in serum of model rats were further increased in each Fuzi group,while the content of Ca^(2+)was decreased(P<0.05 or P<0.01).Compared with JY group,BNP content in BT and SX groups was significantly increased(P<0.01),CKMB and LDH levels were significantly increased(P<0.05 or P<0.01),ALD content in SX group was significantly increased(P<0.05).Compared with model group,spleen and thymus indexes in HB and SX group were significantly decreased(P<0.01),lung and liver indexes in JY group were significantly decreased(P<0.05 or P<0.01),and lung indexes in BT group were

关 键 词：附子 不同产地 急性心力衰竭 毒性 

分 类 号：R285.5[医药卫生—中药学]