Guo Zhixin, Zhao Zhihua
Department of Endocrinology, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, PR China.
Eur J Pharmacol. 2007 Mar 8;558(1-3):208-13. doi: 10.1016/j.ejphar.2006.11.066. Epub 2006 Dec 12.
This study investigated the effect of N-acetylcysteine on plasma adiponectin, renal adiponectin receptors, lipid metabolism and oxidative stress in streptozotocin-induced diabetic rats. Metabolic parameters, plasma adiponectin level, renal protein expression of adiponectin receptors were analyzed in controls and diabetic rats treated with or without N-acetylcysteine in drinking water for 8 weeks. Plasma lipid, creatinine and free 5-F(2t)-isoprostane levels, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal connective tissue growth factor (CTGF) were increased in diabetic rats. The decreased plasma adiponectin levels and renal protein expression of adiponectin receptor 1 were accompanied by the decreased renal phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK)-alpha (Thr172) and protein expression of phospho-acetyl coenzyme A carboxylase (ACC) (Ser79) which led to the increased renal triglyceride levels in diabetic rats. There was no difference in the protein expression of renal adiponectin receptor 2 between control and diabetic rats. N-acetylcysteine treatment attenuated the increased oxidative stress, plasma and renal lipids, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal CTGF, but did not affect plasma adiponectin levels, renal protein expression of adiponectin receptor 1, phosphorylation of AMPK-alpha (Thr172) and renal protein expression of phospho-ACC (Ser79) in diabetic rats. These results suggested that the decreased plasma adiponectin and renal adiponectin receptor 1 result in the increased renal triglyceride that stimulates renal CTGF expression leading to the renal hypertrophy and the deteriorated renal function in the diabetic rats. N-acetylcysteine treatment attenuates the increased oxidative stress, but has no effect on the decreased plasma adiponectin and renal adiponectin receptor 1 in diabetic rats, indicating that oxidative stress may not contribute to the decreased plasma adiponectin and renal adiponectin receptor 1 protein expression in diabetic rats.
本研究调查了N-乙酰半胱氨酸对链脲佐菌素诱导的糖尿病大鼠血浆脂联素、肾脂联素受体、脂质代谢及氧化应激的影响。对对照组以及饮用含或不含N-乙酰半胱氨酸的水8周的糖尿病大鼠的代谢参数、血浆脂联素水平、脂联素受体的肾蛋白表达进行了分析。糖尿病大鼠的血浆脂质、肌酐及游离5-F(2t)-异前列腺素水平、尿蛋白排泄率、系膜基质扩张指数以及肾结缔组织生长因子(CTGF)的蛋白表达均升高。血浆脂联素水平降低以及脂联素受体1的肾蛋白表达降低，同时伴有糖尿病大鼠肾中腺苷单磷酸(AMP)-激活的蛋白激酶(AMPK)-α(苏氨酸172)磷酸化水平降低以及磷酸化乙酰辅酶A羧化酶(ACC)(丝氨酸79)蛋白表达降低，这导致糖尿病大鼠肾甘油三酯水平升高。对照组与糖尿病大鼠之间肾脂联素受体2的蛋白表达无差异。N-乙酰半胱氨酸治疗减轻了氧化应激增加、血浆及肾脂质、尿蛋白排泄率、系膜基质扩张指数以及肾CTGF蛋白表达，但对糖尿病大鼠的血浆脂联素水平、脂联素受体1的肾蛋白表达、AMPK-α(苏氨酸172)磷酸化以及磷酸化ACC(丝氨酸79)的肾蛋白表达无影响。这些结果表明，血浆脂联素及肾脂联素受体1降低导致肾甘油三酯增加，刺激肾CTGF表达，进而导致糖尿病大鼠肾肥大及肾功能恶化。N-乙酰半胱氨酸治疗减轻了氧化应激增加，但对糖尿病大鼠血浆脂联素降低及肾脂联素受体1无影响，表明氧化应激可能与糖尿病大鼠血浆脂联素及肾脂联素受体1蛋白表达降低无关。
