摘要
目的探讨法舒地尔(Rho激酶抑制剂)对急性氧乐果中毒大鼠心肌损害的保护作用及机制。方法将40只雄性SD大鼠随机分为正常对照组(NC组)、中毒组(OM组)、阿托品治疗组(AT组)和阿托品+法舒地尔联合治疗组(UN组),每组10只大鼠。采用腹腔注射氧乐果制备急性有机磷农药中毒模型,染毒后给予阿托品或阿托品+法舒地尔的不同治疗,观察48 h各组大鼠存活状况、中毒症状消失时间、心肌病理变化,检测心肌细胞凋亡和心肌组织Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤/白血病-2(Bcl-2)蛋白表达情况。结果 OM组大鼠短时间[(29.0±6.3)m in]全部死亡;AT组有3只大鼠死亡,平均死亡时间(23.3±2.1)h;UN组有1只大鼠于28 h时死亡;NC组大鼠无死亡。4组大鼠死亡率比较,差异有统计学意义(P<0.01)。AT组与UN组大鼠呼吸困难消失时间比较,差异无统计学意义(P>0.05);两组大鼠肌力0分与肌颤消失时间比较,差异均有统计学意义(P<0.01)。与NC组比较,AT组、UN组心肌病理损害明显,心肌细胞凋亡显著增加,心肌组织Bax蛋白表达增加,Bcl-2蛋白表达减少,Bax/Bcl-2比值升高,心肌细胞凋亡率(AI)升高,差异均有统计学意义(P<0.01)。与NC组比较,OM组心肌病理损害不明显,心肌组织Bcl-2蛋白表达减少(P<0.05);而Bax蛋白表达、Bax/Bcl-2比值及心肌细胞AI间差异均无统计学意义(P>0.05)。与AT组比较,UN组心肌病理损害减轻,心肌细胞凋亡减少,Bax蛋白表达减少,Bcl-2蛋白表达增加,Bax/Bcl-2比值下降,心肌细胞AI降低,差异均有统计学意义(P<0.01)。结论法舒地尔能明显减轻急性氧乐果中毒大鼠的中毒症状,明显减轻心肌损害,降低中毒大鼠的死亡率;能显著抑制氧乐果诱导心肌组织Bax/Bcl-2蛋白比值的升高,进而抑制心肌细胞凋亡。法舒地尔对急性氧乐果中毒大鼠的心肌损害具有明显的保护作用。
Objective To study the protective effects of fasudil（a Rho-kinase inhibitor） on the myocardium in rats with acute omethoate poisoning and its mechanism.Methods Forty male SD rats were divided randomly into groups normal control（NC）,omethoate poisoning（OM）,atropine treatment（AT） and atropine plus fasudil（UN）,10 in each.Omethoate was injected intraperitoneally to establish acute organophosphorus pesticide poisoning models.After exposure,atropine or atropine plus fasudil was given.The survival,time of poisoning symptom disappearing,cardiac pathological changes were observed in all groups at hours 48;myocardial apoptosis and myocardial tissue Bcl-2-related X protein（Bax）,the expressions of B cell lymphoma/leukemia-2（Bcl-2） protein determined.Results All rats died in OM group within（29.0±6.3） min;3 died in AT group,the average time of death was（23.3 ± 2.1） h;1 died in UN group at hours 28,no rat died in NC group;the difference was significant（P0.01）.No significant difference was noted in time of dyspnea disappearing between groups AT,UN（P0.05）,but there was in muscle strength scored 0 and amyostasia disappearing（P0.01）.When compared with group NC,groups AT and UN had obvious pathological lesions,increased cardiomyocyte apoptosis,elevated Bax protein expression,decreased Bcl-2 protein expression,increased Bax/Bcl-2 ratio and rate of myocardial apoptosis（AI）,the difference was significant（P0.01）.When compared with group NC,OM group had unmarked myocardial injury,Bcl-2 expression decreased（P0.05）,but no difference was noted in Bax protein expression,Bax/Bcl-2 ratio,myocardial cell AI（P0.05）.When compared with AT group,group UN had fewer myocardial injuries,decreased myocardial apoptosis and Bax protein expression,increased Bcl-2 protein expression,reduced Bax/Bcl-2 ratio and AI,the difference was significant（P0.01）.Conclusion Fasudil can improve effectively the acute omethoate poisoning symptoms,reduce myocardial injuries and mortality,inhibit remarkably omethoate-induced elevated Bax/Bcl-2 ratio,thus to inhibit myocardial apoptosis.Fasudil has obvious protective effect on myocardium in acute omethoate poisoning rats.
出处
《中国全科医学》
CAS
CSCD
北大核心
2010年第24期2758-2762,共5页
Chinese General Practice
基金
徐州市社会发展基金资助项目(XM08C091)
关键词
中毒
氧乐果
心肌损害
细胞凋亡
法舒地尔
Poisoning
Omethoate
Myocardial damage
Cell apoptosis
Fasudil
