慢性硫酸锰染毒对大鼠心肌组织的损害

Effects of chronic manganese sulfate toxicity test on myocardial ultrastructure and heart organ index of rats

目的 观察硫酸锰对大鼠血压、心肌组织的影响,并探讨剂量-反应关系.方法 将40只SPF级SD大鼠随机分为空白对照组（生理盐水）和硫酸锰5、15、25 mg/kg剂量组,每组10只.腹腔注射硫酸锰染毒,每周5次,共6个月.无创尾套法测量大鼠的血压,计算大鼠的心脏脏器系数,每组随机选择3只大鼠进行心肌超微结构观察,用基准剂量Benchmark Dose（BMD）法评估硫酸锰注射剂量与心脏脏器系数改变之间的BMD及基准剂量95％可信区间下限（BMDL）.结果 4组大鼠血压的差异无统计学意义（P＞0.05）.空白对照组、5、15、25 mg/kg剂量组大鼠心脏脏器系数分别为0.24％±0.10％,0.25％±0.02％,0.26％±0.02％,0.24％±0.02％,其中对照组与15 mg/kg剂量组的心脏脏器系数的差异有统计学意义（F=3.25,P=0.015）.大鼠心肌超微结构观察,各染毒组均出现不同程度的线粒体超微结构改变及心肌纤维退行性变,其中线粒体表现为水肿、空泡样变及嵴消失;心肌纤维表现为肌纤维排列疏松,肌束紊乱及肌束断裂.在慢性硫酸锰染毒与心脏脏器系数的剂量-反应关系研究中,硫酸锰的BMD及BMDL分别为9.33和4.28 mg/kg.结论 慢性锰染毒可使大鼠心肌组织出现损伤效应.

Objective To observe the effects of manganese sulfate on blood pressure、myocardial ultrastructure and heart organ index of rats.Methods Forty male SPF SD rats were randomly divided into 4 groups：control group （0 mg/kg）,5 mg/kg dose group,15 mg/kg dose group and 25 mg/kg dose group,10 rats each group.Intraperitoneal injection was performed for six months,by five times each week,the rat blood pressure was measured by tail cuff method,and the heart organ index of the rats was computed.Three rats were selected from each group randomly,and the myocardial ultrastructure of the rats was observed by using transmission electron microscopy （TEM）.The BMD and BMDL between manganese sulfate injected dose and the rats heart organ index were evaluated by BMD （Benchmark Dose）.Results There was no significant of blood pressure between the experimental group and the control group （P＞0.05）.The heart organ indexes of the four groups were 0.24％±0.10％,0.25％±0.02％,0.26％±0.02％,and 0.24％±0.02％.Statistical significance of heart organ indexes was found between the 15 mg/kg dose group and the control group （P＜0.05）.Observed by TEM,we found that-different degrees of mitochondrial crest fracture or disappear,mitochondria swelling,hydropic change and myocardial fibers degeneration happened in the rats of the three exposed groups,but not the control group.The BMD and BMDL were calculated as 9.33 mg/kg and 4.28 mg/kg in the study of manganese sulfate injected dose and the rats heart organ index.Conclusion Chronic manganese poisoning can lead to myocardial mitochondria superfine lesions,myocardial fiber damage and heart organ index change in rats.