法舒地尔对急性氧乐果染毒大鼠心肌细胞的影响  

Effect of fasudil of on rat cardiomyocytes acutely exposed to omethoate

作　　者：燕宪亮[1] 黄炜[2] 程江华[3] 王厚清[1] 许铁[1] 

机构地区：[1]徐州医学院附属医院急救中心麻醉学院急救医学教研室,221006 [2]徐州医学院附属医院内科心血管科,221006 [3]浙江省金华市中心医院急诊科

出　　处：《中华劳动卫生职业病杂志》2012年第9期656-660,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：徐州市科技局社会发展基金（XM08C091）;徐州医学院附属医院科技基金（2011175）;徐州医学院附属医院优秀青年骨干基金（2011121）

摘　　要：目的采用氧乐果染毒的离体培养心肌细胞模型，观察法舒地尔对染毒心肌细胞的影响及其可能机制。方法分离雄性SD大鼠心肌细胞，DMEM中常规培养。按培养基中氧乐果及法舒地尔剂量，分为不同剂量组培养，在3、6、12及24h时，测定各组心肌细胞的存活率，根据各组心肌细胞的存活率，选取中剂量染毒组和中剂量治疗组进行心肌细胞收缩幅度测定，并检测培养基中的乳酸脱氢酶（LDH）活力及心肌细胞Bcl-2和Bax蛋白的表达水平。结果与正常对照组比较，各染毒组心肌细存活率均明显降低，且随染毒剂量增高，心肌细胞存活率呈降低趋势，差异均有统计学意义（P〈0．01）。与正常对照组比较，中剂量染毒组和中剂量治疗组各时点心肌细胞的收缩幅度明显降低，差异有统计学意义（P〈0．01），与中剂量染毒组比较，中剂量治疗组12h及24h心肌细胞收缩幅度增大，差异有统计学意义（P〈0．01）。中剂量染毒组和中剂量治疗组培养基中LDH活力[（224．9±14．7）、（156．0±6．8）U／L]明显高于正常对照组[（59．2±6．5）U／L]，中剂量治疗组LDH活力明显低于中剂量染毒组，差异均有统计学意义（P〈0．01）。与正常对照组比较，中剂量染毒组和中剂量治疗组Bcl-2蛋白表达明显降低，中剂量染毒组Bax蛋白表达明显增高，差异均有统计学意义（P〈0．01）。与中剂量染毒组比较，中剂量治疗组Bcl-2蛋白表达明显增高，Bax蛋白表达明显降低，差异有统计学意义（P〈0．01）。结论法舒地尔能抑制氧乐果诱导凋亡调节蛋白Bax、Bcl-2的异常表达，这可能是其减轻氧乐果对心肌细胞的损害的机制之一。Objective To investigate the effect of fasudil on in vitro cultured cardiomyocytes （CMs） exposed to omethoate and its possible mechanism. Methods Cardiomyocytes were isolated from male SD rats and were then cultured in DMEM conventionally. The CMs were divided into different groups based on the doses of omethoate and fasudil in culture media. After 3, 6, 12, and 24 h of culture, the survival rate of CMs in each group was measured, the CMs in the medium-dose omethoate and medium-dose fasudil groups were subject to shortening amplitude measurement, and the content of lactate dehydrogenase （LDH） in culture media and expression of Bcl-2 and Bax in CMs were measured. Results Compared with the normal control group, each omethoate group showed significantly lower survival rate of CMs, which was negatively correlated with the dose of omethoate （P〈0.01）. Compared with the normal control group, the medium-dose omethoate and medium-dose fasudil groups showed significantly decreased shortening amplitudes of CMs at all time points （P〈0.01）, and the shortening amplitudes of CMs were significantly higher in the medium-dose fasudil group than in the medium- dose omethoate group after 12 h and 24 h of cuhure （P〈0.01）. The LDH level was significantly higher in the medium- dose omethoate and medium-dose fasudil groups than in the normal control group, and the medium-dose fasudil group showed significantly lower LDH level than the medium-dose omethoate group （P〈0.01）. Compared with those in the normal control group, the Bcl-2 expression in the medium-dose omethoate and medium-dose fasudil groups was decreased significantly, and the Bax expression in the medium-dose omethoate group was increased significantly （P〈0.01）. Compared with the medium-dose omethoate group, the medium-dose fasudil group had significantly increased Bcl-2 expression and significantly decreased Bax expression （P〈0.01）. Conclusion Fasudil can inhibit the abnormal expression of apoptosis regulatory proteins （Bcl-2 and

关 键 词：杀虫药 有机磷 细胞培养 存活率 

分 类 号：R285.5[医药卫生—中药学]