丁胱亚磺酰亚胺排空组织谷胱甘肽对大鼠心肌谷胱甘肽系统的影响

Effect of Glutathione Depletion on Glutathione System in Myocadium of Rat

目的 :观察采用谷氨酰半胱氨酸合成酶抑制剂———丁胱亚磺酰亚胺 (BSO)排空大鼠心肌谷胱甘肽 (GSH)是否影响大鼠心肌组织GSH的稳态 ,以及是否对GSH代谢相关酶活性及mRNA表达产生影响。方法 :采用长时间力竭运动、注射BSO排空GSH两种实验模型 ,比较对照组与注射BSO组SD大鼠心肌在静息状态和长时间力竭运动后GSH状态及其代谢变化。结果 :注射BSO 8天后 ,大鼠心脏GSH含量分别为对照组的 6 % ,且GSH的下降伴随着氧化型谷胱甘肽 (GSSG)的下降 ,GSH/GSSG的比值无显著变化。GSH排空导致GSH代谢酶活性发生适应性变化 ,注射BSO后心肌中谷胱甘肽过氧化物酶 (GPX)活性与对照组相比显著下降 (P <0 .0 0 1)。注射BSO组与对照组相比 ,心肌谷氨酰转肽酶 (GGT)活性显著增加 (P <0 .0 5 )。注射BSO力竭组与注射BSO组相比 ,心肌GGT活性显著增加 (P <0 .0 0 1) ,心肌注射BSO抑制γ -谷氨酰半胱酸合成酶 (GCS)活性 ,注射BSO力竭组大鼠心肌GCSmRNA表达量高于注射BSO组 ,表明极度排空谷胱甘肽后 ,GCSmR NA表达量的增加可能是机体产生的应激反应。

Purpose To study the effect of chronic glutathione (GSH) depletion in vivo by injection of L-buthione- -sulfoximine (BSO) on the balance of intracellular and interorganic GSH and on the several enzymes activity in GSH regulation and GCSmRNA expression. Methods In experimental models of exhaustive exercise and depletion of GSH by injecting BSO, GCS mRNA expression was tested using reverse transcription-polymerase chain reaction (RT-PCR) technical. Results 8-day BSO treatment decreased concentrations of GSH in the myocardium to 6% of the normal levels. This decrease was paralleled with a concomitant decrease of glutathione disulfide (GSSG),and thus the GSH/GSSG ratio was maintained. GSH depletion caused adaptive changes in several enzymes involved in GSH regulation: glutathione peroxidase of BSO group in myocardium decreased as compared with control group. Myocardium γ-glutamyltranspeptidase activity of BSO group increased as compared with control group (P < 0.05). Myocardium γ-glutamyltranspeptidase activity of BSO exhausted group increased as compared with BSO group (P < 0.001). Conclusion Although GCS activity is restrained by BSO, but GCS mRNA expression increased. It was showed that there was an adaptation to reactive stress.