基于“有故无殒”理论的健康与慢性心力衰竭状态下附子对小鼠心脏不同作用的实验研究  

Experimental research of different effects of Fuzi on the heart of healthy and chronic heart failure mice based on the"Yougu Wuyun"theory

作　　者：钱嘉豪 吴美平[1] 凌望 陈丽雯 陈静[1] 柴钰 QIAN Jiahao;WU Meiping;LING Wang;CHEN Liwen;CHEN Jing;CHAI Yu(Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属市中医医院,上海200071 [2]上海中医药大学附属龙华医院,上海200032

出　　处：《上海中医药杂志》2024年第10期71-78,共8页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973826)。

摘　　要：目的基于中医经典“有故无殒”理论,探讨附子水煎液对健康小鼠及慢性心力衰竭小鼠心脏的不同作用。方法将SPF级别8周龄C57BL/6J品系雄性小鼠随机分为对照组(Ctrl)、附子组(FZH)、多柔比星组(Dox)、多柔比星加附子组(Dox+FZH)。分别给予Dox小鼠和Dox+FZH小鼠每3天腹腔注射5 mg/kg多柔比星,Ctrl与FZH给予等体积氯化钠溶液(9 g/L)腹腔注射,实验开始第1天给予Dox、Dox+FZH小鼠5 mg/kg多柔比星腹腔注射后,分别给FZH与Dox+FZH小鼠每日2 g/kg附子灌胃,Ctrl与Dox小鼠分别使用等体积氯化钠溶液(9 g/L)灌胃,造模周期共4周。观察小鼠的一般情况,对小鼠生存率、心质量、体质量、心质量比、心胫比及心超指标等进行统计,分析小鼠心脏组织及血清中脑利尿钠肽(BNP)和心肌肌钙蛋白Ⅰ(cTnⅠ)的含量,并检测心脏组织中凋亡相关蛋白的表达情况,观察小鼠心脏组织切片单个心肌细胞横截面积大小,评估附子对健康和慢性心力衰竭状态下小鼠心肌损伤的影响。结果(1)健康状态下,Ctrl和FZH小鼠被毛毛色光亮,形体匀称,四肢活动正常且Ctrl和FZH小鼠均未见死亡;与Ctrl比较,FZH小鼠的心质量、心质量比、心胫比、左室射血分数、左室短轴缩短率、心率、收缩期左室后壁厚度均降低(P<0.05),左室舒张末期内径升高(P<0.05);与Ctrl比较,FZH小鼠活化后的半胱氨酸蛋白3(Cleaved-Caspase3)表达升高(P<0.05),B-细胞淋巴瘤因子2蛋白/Bcl2关联X蛋白(Bcl2/Bax)比值降低(P<0.05);血清中BNP和cTnⅠ的含量差异无统计学意义(P>0.05);小鼠心脏组织切片单个心肌细胞横截面积相应缩小(P<0.05)。与Ctrl比较,FZH小鼠心房利尿钠肽(ANP)基因表达升高(P<0.05)。(2)慢性心力衰竭状态下,Dox小鼠毛色晦暗,形体消瘦,活动迟缓,进食量减少,而Dox+FZH小鼠活动能力和进食情况均较Dox有所改善;Dox共计死亡6只,Dox+FZH小鼠死亡3只,附子可以改善病理状态小鼠生存率�Objective Based on the classic traditional Chinese medicine(TCM)theory of"Yougu Wuyun(existing defects without causing fatality)",the study aimed to explore the different effects of Fuzi(Aconiti Lateralis Radix Praeparata)decoction on the heart of both healthy and chronic heart failure mice.Methods Eight-week-old male SPF C57BL/6J mice were randomly divided into control group(Ctrl),Fuzi group(FZH),doxorubicin group(Dox),and doxorubicin plus Fuzi group(Dox+FZH).Mice in Dox and Dox+FZH groups received intraperitoneal injections of 5 mg/kg doxorubicin every 3 days.Mice in Ctrl and FZH groups received equivalent volumes of saline(9 g/L)intraperitoneally.On the first day of the experiment,mice in Dox and Dox+FZH groups received intraperitoneal injections of 5 mg/kg doxorubicin,followed by daily gavage with 2 g/kg Fuzi Decoction for mice in FZH and Dox+FZH groups.Mice in Ctrl and Dox groups were gavaged with an equivalent volume of normal saline solution(9 g/L).The modeling period lasted for 4 weeks.The general condition of the mice was observed,and survival rate,heart weight,body weight,heart weight ratio,heart-to-tibia length ratio,and echocardiographic parameters were statistically analyzed.The levels of brain natriuretic peptide(BNP)and cardiac troponin I(cTnI)in cardiac tissue and serum of mice were measured.Apoptosis-related protein expression in heart tissue was detected,and the cross-sectional area of individual cardiomyocytes was observed to assess the effects of Fuzi on myocardial injury in healthy and chronic heart failure mice.Results①In a healthy state,mice in Ctrl and FZH groups had shiny fur,proportional body shape,and normal limb movement,with no deaths observed in either group.Compared with mice in Ctrl group,mice in FZH group showed a decrease in heart weight,heart weight ratio,heart-to-tibia length ratio,left ventricular ejection fraction,left ventricular fractional shortening,heart rate,and systolic left ventricular posterior wall thickness(P<0.05),along with an increase in left ventricular end-di

关 键 词：附子 慢性心力衰竭 中医理论 中药 毒效研究 安全用药 

分 类 号：R285.5[医药卫生—中药学]