α-硫辛酸对糖尿病大鼠肾脏线粒体的保护作用。
The protective effect of α-Lipoic acid on mitochondria in the kidney of diabetic rats.
作者信息
Wang Li, Wu Chen-Guang, Fang Chun-Qian, Gao Jing, Liu Ying-Zhao, Chen Yan, Chen Yu-Ning, Xu Zhi-Gang
机构信息
Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu 212002, China.
出版信息
Int J Clin Exp Med. 2013;6(2):90-7. Epub 2013 Jan 26.
BACKGROUND
Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes and the leading cause of end-stage renal disease. Recent research has found that oxidative stress participates in the development of diabetic nephropathy. α-lipoic acid (α-LA), a powerful antioxidant, plays an important role in renal protection against DN, but the underlying mechanism remains unknown. This study modeled the renal protective effects of α-lipoic acid in streptozotocin (STZ) induced diabetic rats and explore the underlying mechanism, which provides new theoretical bases for clinical treatment of diabetic nephropathy.
METHODS
The diabetic model was induced by intraperitoneal injection of STZ on Male SD and then the diabetic rats were randomly divided into two groups: untreated-diabetic group (DM group), α-LA treated-diabetic group (α-LA group), and the normal rats served as control group (NC group). After 8 weeks of STZ induction, Blood glucose (BG), Blood Urea Nitrogen (BUN), Serum Creatinine (SCr) and urinary albumin excretion rate (UAER) were examined, and morphological changes were assessed by histology. The levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) were also evaluated in serum and renal cortex. Additionally, kidney mitochondrial membrane potential and mitochondrial swelling were measured for different groups. The expression of voltage-dependent anion channel (VDAC) on mitochondria were evaluated by both Western blotting and Immunohistochemistry.
RESULTS
After 8 weeks induction of STZ, significant reductions in BUN, SCr, UAER (P<0.01 or P<0.05) and histological improvement were observed in the α-LA group compared to the DM group. In the serum and renal cortex of α-LA group, the content of MDA and the activities of SOC were both significantly decreased (P<0.05). Compared to the DM group, the mitochondrial membrane potential in the α-LA group was significantly increased (P<0.05) and mitochondrial swelling was reduced. Meanwhile, the expression of VDAC on mitochondrial was significantly increased (P<0.05) in the α-LA group.
CONCLUSION
Our findings indicate that antioxidant α-LA exerts a protective role against the development of DN, and the underlying mechanism may involve effective suppression of the generation of oxidants, protection of mitochondrial function, and up-regulating of VDAC expression.
背景
糖尿病肾病（DN）是糖尿病最常见的慢性并发症之一，也是终末期肾病的主要原因。最近的研究发现氧化应激参与糖尿病肾病的发展。α-硫辛酸（α-LA）是一种强大的抗氧化剂，在肾脏保护免受糖尿病肾病方面发挥重要作用，但其潜在机制尚不清楚。本研究建立了α-硫辛酸对链脲佐菌素（STZ）诱导的糖尿病大鼠的肾脏保护作用模型，并探讨其潜在机制，为糖尿病肾病的临床治疗提供新的理论依据。
方法
雄性SD大鼠腹腔注射STZ诱导糖尿病模型，然后将糖尿病大鼠随机分为两组：未治疗糖尿病组（DM组）、α-LA治疗糖尿病组（α-LA组），正常大鼠作为对照组（NC组）。STZ诱导8周后，检测血糖（BG）、血尿素氮（BUN）、血清肌酐（SCr）和尿白蛋白排泄率（UAER），并通过组织学评估形态学变化。还评估了血清和肾皮质中丙二醛（MDA）水平和超氧化物歧化酶（SOD）活性。此外，测量了不同组的肾线粒体膜电位和线粒体肿胀情况。通过蛋白质印迹法和免疫组织化学法评估线粒体上电压依赖性阴离子通道（VDAC）的表达。
结果
STZ诱导8周后，与DM组相比，α-LA组的BUN、SCr、UAER显著降低（P<0.01或P<0.05），组织学得到改善。在α-LA组的血清和肾皮质中，MDA含量和SOD活性均显著降低（P<0.05）。与DM组相比，α-LA组的线粒体膜电位显著升高（P<0.05），线粒体肿胀减轻。同时，α-LA组线粒体上VDAC的表达显著增加（P<0.05）。
结论
我们的研究结果表明，抗氧化剂α-LA对糖尿病肾病的发展具有保护作用，其潜在机制可能包括有效抑制氧化剂的产生、保护线粒体功能以及上调VDAC表达。
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