多柔比星致心力衰竭大鼠血浆及心肌组织内源性硫化氢变化的意义  

Significance of Changes of Endogenous Hydrogen Sulfide in Rats with Doxorubicin-Induced Heart Failure

作　　者：苏钰雯[1] 杜军保[1] 韩薇[1] 张前进[2] 张春雨[1] 唐朝枢[3] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院中医科,北京100034 [3]北京大学第一医院心血管病研究所,北京100034

出　　处：《实用儿科临床杂志》2006年第19期1312-1313,1335,共3页Journal of Applied Clinical Pediatrics

基　　金：国家杰出青年科学基金项目资助(30425010);国家重点基础研究发展规划项目资助(G2000056905)

摘　　要：目的研究多柔比星致心力衰竭大鼠血浆及心肌组织内源性硫化氢(H2S)水平差异,以探讨其在心力衰竭发病中的意义。方法雄性Wistar大鼠21只,随机分为2组。1.多柔比星组(n=12):腹腔注射多柔比星(粉针剂),2.5 mg/(kg.次),1次/周,共用10周;2.对照组(n=9):用相同容量生理盐水代替多柔比星,给药方法同多柔比星组。观察两组大鼠行为体征变化,于第10周检测大鼠心功能和血流动力学指标,并采用硫敏感电极法测定其血浆及心肌组织H2S水平,比较其差异。结果多柔比星组大鼠死亡率为33%,余表现为萎靡不振,活动、进食减少,呼吸加快,体温下降,体质量明显减轻,且左室收缩压(LVSP)、左室内压差[△LVP=LVSP-左室舒张压(LVDP)]、左室内压最大上升速率(+dp/dtmax)及最大下降速率(-dp/dtmax)明显降低(P均<0.01),LVDP、左心室质量/体质量(LVW/BW)指数和全心质量/体质量(HW/BW)指数较对照组明显升高(P均<0.01);多柔比星组血浆及心肌组织H2S水平分别低于对照组[血浆(32.32±2.57)μmol/Lvs(49.15±3.42)μmol/L;心肌组织(10.96±3.96)μmol/Lvs(20.22±3.03)μmol/L],差异有显著性(P均<0.001)。结论在大鼠多柔比星所致心力衰竭过程中内源性H2S生成下降。Objective To investigate the changes in hydrogen sulfide（H2S） level in plasma and myocardial tissues of doxorubicin - induced heart failure rats,and to study the role of H2S in the development of doxorubicin induced heart failure. Methods Male Wistar rats were randomly divided into 2 groups as follows： the doxombicin group（ n = 12）, in which 2.5 mg/kg of doxorubicin was injected intraperitoneal once a week for 10 weeks（total dose of 25 mg/kg） ; the control group（ n = 9）, in which an equivalent volume of physiological .saline was administered weekly for a total of 10 weeks. The observation of behavior was taken at the same time. Hemodynamic and echocardiographic measurements were obtained 10 weeks after treatment. Meanwhile, H2S concentrations in serum and myocardial tissues were evaluated by modified sulfide electrode method. The changes of H2S level between 2 groups were analyzed. Results The rats treated with doxorubicin showed inanimate behavior, decrease of the body temperature, activities and food intake, faster breathing, significant loss of weight, the cumulative mortality was 33 %. Left ventricular systolic pressure （LVSP）, difference of left ventricular pressure [△LVP = LVSP- left ventricular diastolic pressure（LVDP）] and left ventricular peak rate of contraction （ ± LV dp/dtmax）, left ventricular peak rate of relaxation（ - LV dp/dtmax）were significantly reduced in the group of doxombicin rats（ P〈 0.01 ）. LVDP, the ratio of left ventricular weight/body weight（LVW/BW） and the ratio of heart weight/body weight（HW/BW） were significantly increased in doxorubicin group（all P〈0.01 ）. The plasma level of HaS and HaS concentration in myocardial tissues of rats in doxorubicin group were both significantly decreased as compared with those in the control group [ （32.32 ± 2.57 ） pmol/L vs （49.15 ± 3.42 ） μmol/l, and （10.96 ± 3.96） μmol/L vs （20.22 ± 3.03 ） μmol/L, all P 〈 0.001 ]. Conclusion Endogenous HaS decreases in the development

关 键 词：硫化氢 多柔比星 心力衰竭 大鼠 

分 类 号：R541.6[医药卫生—心血管疾病]