Hida W, Shindoh C, Satoh J, Sagara M, Kikuchi Y, Toyota T, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1875-9. doi: 10.1164/ajrccm.153.6.8665049.
We examined whether streptozotocin (STZ)-induced diabetic rats have an impairment in diaphragm contractility, and if so, whether N-acetylcysteine (NAC), a nonspecific antioxidant, prevents this impairment. First, diaphragm contractility, assessed by tension-frequency relationships and twitch kinetics in in vitro diaphragm strip preparations of Wistar rats, was obtained on Days 3 and 7 after administration of STZ of 30 or 60 mg/kg body weight, and compared with that of the control group. Second, NAC at 500 mg/kg body weight or vehicle solution was administered orally every day in rats treated with STZ at 60 mg/kg body weight, and diaphragm function on Day 7 after starting NAC treatment was compared between vehicle control and STZ-treated groups. We found that diaphragm function in STZ-treated rats, which had hyperglycemia, decreased in a dose- and time-dependent manner. NAC inhibited the decrease in diaphragm contractility in STZ-treated rats without reducing blood glucose. These findings suggest that the loss of diaphragm function in STZ-induced diabetic rats is not directly related to hyperglycemia. The data are consistent with secondary alterations of normal cytokine signaling or changes in the redox state of the cell, both of which could be affected by NAC treatment.
我们研究了链脲佐菌素（STZ）诱导的糖尿病大鼠膈肌收缩力是否受损，如果受损，非特异性抗氧化剂N-乙酰半胱氨酸（NAC）是否能预防这种损伤。首先，通过Wistar大鼠体外膈肌条制备中的张力-频率关系和抽搐动力学评估膈肌收缩力，在给予30或60mg/kg体重的STZ后第3天和第7天获得，并与对照组进行比较。其次，在以60mg/kg体重的STZ处理的大鼠中，每天口服500mg/kg体重的NAC或赋形剂溶液，并比较赋形剂对照组和STZ处理组在开始NAC处理后第7天的膈肌功能。我们发现，患有高血糖的STZ处理大鼠的膈肌功能呈剂量和时间依赖性下降。NAC抑制了STZ处理大鼠膈肌收缩力的下降，而不降低血糖。这些发现表明，STZ诱导的糖尿病大鼠膈肌功能丧失与高血糖没有直接关系。数据与正常细胞因子信号传导的继发性改变或细胞氧化还原状态的变化一致，这两者都可能受到NAC处理的影响。
