中国药物警戒
中國藥物警戒
중국약물경계
CHINESE JOURNAL OF PHARMACOVIGILANCE
2015年
8期
449-453
,共5页
附子%脾肾阳虚%心衰%功效%毒性
附子%脾腎暘虛%心衰%功效%毒性
부자%비신양허%심쇠%공효%독성
Radix Aconiti Lateralis Praeparata%spleen-kidney yang deficiency%heart failure%efficacy%toxicity
目的：通过附子水煎剂对脾肾阳虚型心衰大鼠“强心”功效及心脏毒性的研究，探讨附子在大鼠病证结合模型上针对心脏靶器官的功效-毒性表达的关联性。方法采用皮下注射异丙肾上腺素建立大鼠慢性心力衰竭模型，灌胃大黄粉悬液建立脾肾阳虚模型；造模同时灌胃不同剂量的附子水煎剂，连续9 d。测试各组大鼠实验前后的心电图和血流动力学，对大鼠心、左心室、脑、肝、脾和肾称重并计算脏器系数，检测血清中 N 末端脑钠钛前体（NT-pro BNP）、高敏 C 反应蛋白（hs-CRP）、天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）和心肌肌钙蛋白（cTn-I）的活力。结果附子水煎剂在1.35~5.40 g·kg-1能显著抑制脾肾阳虚型心衰大鼠的 T 波升高、心率减慢和 QRS 间期延长（P <0.05），升高脾肾阳虚型心衰型大鼠的 LVSP、±dp/dtmax 和血清中 AST、LDH 和 cTn-I 的水平（P <0.05），并能降低 LVEDP 和血清中NT-pro BNP、hs-CRP 的水平（P <0.05），增大心系数和左心室系数（P <0.05），并呈现一定的剂量依赖性。结论附子水煎剂在1.35~5.40 g·kg-1剂量范围内，对脾肾阳虚型心衰大鼠的“温补脾阳”、“回阳救逆”的功效表达同时也表达了心脏毒性，提示附子基于心脏的“效-毒”关联评价对保证附子临床强心功效的安全应用有重要的意义。
目的：通過附子水煎劑對脾腎暘虛型心衰大鼠“彊心”功效及心髒毒性的研究，探討附子在大鼠病證結閤模型上針對心髒靶器官的功效-毒性錶達的關聯性。方法採用皮下註射異丙腎上腺素建立大鼠慢性心力衰竭模型，灌胃大黃粉懸液建立脾腎暘虛模型；造模同時灌胃不同劑量的附子水煎劑，連續9 d。測試各組大鼠實驗前後的心電圖和血流動力學，對大鼠心、左心室、腦、肝、脾和腎稱重併計算髒器繫數，檢測血清中 N 末耑腦鈉鈦前體（NT-pro BNP）、高敏 C 反應蛋白（hs-CRP）、天門鼕氨痠氨基轉移酶（AST）、乳痠脫氫酶（LDH）和心肌肌鈣蛋白（cTn-I）的活力。結果附子水煎劑在1.35~5.40 g·kg-1能顯著抑製脾腎暘虛型心衰大鼠的 T 波升高、心率減慢和 QRS 間期延長（P <0.05），升高脾腎暘虛型心衰型大鼠的 LVSP、±dp/dtmax 和血清中 AST、LDH 和 cTn-I 的水平（P <0.05），併能降低 LVEDP 和血清中NT-pro BNP、hs-CRP 的水平（P <0.05），增大心繫數和左心室繫數（P <0.05），併呈現一定的劑量依賴性。結論附子水煎劑在1.35~5.40 g·kg-1劑量範圍內，對脾腎暘虛型心衰大鼠的“溫補脾暘”、“迴暘救逆”的功效錶達同時也錶達瞭心髒毒性，提示附子基于心髒的“效-毒”關聯評價對保證附子臨床彊心功效的安全應用有重要的意義。
목적：통과부자수전제대비신양허형심쇠대서“강심”공효급심장독성적연구，탐토부자재대서병증결합모형상침대심장파기관적공효-독성표체적관련성。방법채용피하주사이병신상선소건립대서만성심력쇠갈모형，관위대황분현액건립비신양허모형；조모동시관위불동제량적부자수전제，련속9 d。측시각조대서실험전후적심전도화혈류동역학，대대서심、좌심실、뇌、간、비화신칭중병계산장기계수，검측혈청중 N 말단뇌납태전체（NT-pro BNP）、고민 C 반응단백（hs-CRP）、천문동안산안기전이매（AST）、유산탈경매（LDH）화심기기개단백（cTn-I）적활력。결과부자수전제재1.35~5.40 g·kg-1능현저억제비신양허형심쇠대서적 T 파승고、심솔감만화 QRS 간기연장（P <0.05），승고비신양허형심쇠형대서적 LVSP、±dp/dtmax 화혈청중 AST、LDH 화 cTn-I 적수평（P <0.05），병능강저 LVEDP 화혈청중NT-pro BNP、hs-CRP 적수평（P <0.05），증대심계수화좌심실계수（P <0.05），병정현일정적제량의뢰성。결론부자수전제재1.35~5.40 g·kg-1제량범위내，대비신양허형심쇠대서적“온보비양”、“회양구역”적공효표체동시야표체료심장독성，제시부자기우심장적“효-독”관련평개대보증부자림상강심공효적안전응용유중요적의의。
Objective The efficacy and heart toxicity of Aconite's water decoction on spleen-kidney yang deficiency rat with heart failure were studied to explore "efficacy-toxicity" relationship of Aconite on animal models combined disease and syndrome. Methods Chronic heart failure rat model was established with isoprenaline by subcutaneous injection and spleen-kidney yang deficiency rat model was established with rhubarb powder suspension. Rat models were established and Aconite's water decoction was administered simultaneously for 9 consecutive days. Electrocardiogram (ECG) and hemodynamics of rats were measured. Heart, left ventricular, brain, liver, spleen and kidney were weighed and indexes of them were calculated. The activities of N-terminal pro-brain natriuretic peptide (NT-pro BNP), high sensitivity C reactive protein (hs-CRP), aspartate transaminase (AST), lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I) were detected. Results The heart rate of rats dropped, the amplitude of T enlarged and QRS extended after the administration of Aconite's water decoction in the dosage range of 1.35~5.40 g·kg -1. Left ventricular pressure (LVSP) and left ventricular pressure development during isovolumetric contraction/relaxation(± dp/dtmax) elevated and the levels of serum NT-pro BNP and hs-CRP reduced. Heart index and left ventricular index increased. Conclusion Aconite's water decoction in the dosage range of 1.35~5.40 g·kg-1 has certain efficacy on spleen-kidney yang deficiency rat with heart failure, showing that the evaluation on the "efficacy-toxicity"correlation of Radix Aconiti Lateralis has important significance to ensure the safety of clinical cardiac function.
