醋酸铅暴露对雄性大鼠心血管系统功能的影响

Effect of lead acetate exposure on cardiovascular system function in male rats

目的探讨醋酸铅经口暴露对雄性大鼠心血管系统功能的影响。方法 40只SPF级Wistar雄性大鼠随机分为低、中、高3个醋酸铅剂量组灌胃法染毒(分别给予45、90、180 mg/kg醋酸铅),对照组(灌服等量蒸馏水),每组10只,每周5次,共染毒60 d。每组随机选取6只大鼠,尾袖法测定末次染毒12 h后血压和心率水平;末次染毒24 h后摘眼球收集血液,脱颈处死大鼠,分离心脏和胸主动脉。石墨炉原子吸收光谱法测定全血血铅水平;全自动生化分析仪测定外周血血清心肌酶水平;酶联免疫吸附法(ELISA)检测外周血血清氧化应激指标GSH、SOD和MDA水平;HE染色法观察大鼠心脏和胸主动脉组织病理学变化。结果染毒之初各组大鼠体重差异无统计学意义,随染毒时间增加,与对照组相比,各染毒组大鼠体重增长量呈下降趋势;各染毒组大鼠血铅水平均显著高于对照组(P<0.05),且与染毒剂量呈显著正相关(r=0.614,P<0.05);染毒组大鼠收缩压(SBP)水平均显著高于对照组(P<0.05),舒张压、平均动脉压和心率在各组间差异无统计学意义(P>0.05);中、高剂量染毒组大鼠CKMB和C反应蛋白(CRP)水平显著高于对照组,各染毒组大鼠外周血血清LDH和HBDH水平均显著高于对照组(P<0.05),MDA水平显著高于对照组(P<0.01),低、中剂量染毒组大鼠GSH水平低于对照组(P<0.05);病理组织学检查发现,随醋酸铅染毒剂量的增加,大鼠心肌细胞肥大,胞核染色变深,变形、聚集,排列紊乱,心肌间质增宽,并出现炎细胞浸润,心肌纤维多处肿胀断裂,肌横纹消失;胸主动脉未见明显病理变化。结论醋酸铅暴露可引起雄性大鼠的血压升高、心肌酶谱改变及氧化损伤,直接损伤心肌组织。

Objective To investigate the effect of lead acetate exposure on cardiovascular function in male rats. Methods Forty specific pathogen-free male Wistar rats were randomly divided into four groups： three lead exposure groups and a control group. The water solutions with 45, 90 and 180 mg/kg of lead acetate were administered by gavage to rats of exposure groups respectively, five times a week for 60 days ; the rats of control group only received equal volume of water. Blood pressure and heart rate of six rats in each group were determined by tail cuff method 12 h later after last exposure; at the 24 th hour after last exposure, took the blood samples, heart and thoracic aorta after killing the rats by cervical spine dislocation. Blood lead level was determined by graphite furnace atomic absorption spectrometry, serum myocardial enzymes such as CK-MB, LDH, HBDH, AST etc. were measured by automatic biochemical analyzer, and the serum levels of oxidative stress markers such as GSH, SOD and MDA were measured by the oxidative stress kit. Meanwhile, the histopathological changes of heart and thoracic aorta were also observed using HE staining. Results The results showed that the body weight of the lead exposed rats were statistically lowered （P〈0. 001 ） with exposure time compared with the controls, the blood lead levels of lead-exposed rats were higher than the con- trois （P〈0. 05 ）, and was dose-dependent. The rats in lead-exposure groups also had higher systolic blood pressure （SBP） levels than the control group, but the diastolic blood pressure （DBP）, mean arterial pressure （MBP） and heart rate （HR） showed no significant difference with control group （P〉0. 05）. The rats in lead exposed groups had higher serum levels of CKMB, LDH, HBDH, CRP, MDA and lower GSH level than the control group （P〈 0. 05）. Histopathological examination showed myocardial hypertrophy, nuclei hyperchromatic, deformation, aggregation, and derangement, myocardial interstitial broadening, inflammatory cell infiltration along with the increase of lead dose; but the thoracic aortic showed no significant change compared with control group. Conclusion The results suggested that under this experimental conditions, lead acetate may affect the blood pressure and cardiovascular function, induce myocardial enzymes change and oxidative damage, thereby caused direct damage to cardiac muscles.