Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways
Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways
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DOI：
10.1152/ajprenal.00393.2016
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发表时间：
2017-08-01
影响因子：
4.2
通讯作者：
Arya, Dharamvir Singh
中科院分区：
文献类型：
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作者：
Malik, Salma;Suchal, Kapil;Arya, Dharamvir Singh
糖尿病肾病（diabetic nephropathy，DN）是糖尿病的一种微血管并发症，已成为全球性的重要健康问题。有强有力的证据表明，氧化应激，炎症和纤维化在DN的进展中起着关键作用。芹菜素具有抗氧化、抗炎、抗细胞凋亡、抗纤维化和抗糖尿病的特性。因此，我们评估芹菜素是否阻止链脲佐菌素（STZ）诱导的糖尿病大鼠DN的发展和进展。将雄性白化病Wistar大鼠分为对照组、糖尿病对照组、芹菜素治疗组（分别为5-20 mg/kg po）、芹菜素本身（20 mg/kg po）和雷米普利治疗组（2 mg/kg po）。除对照组和自身对照组外，其余各组均单次注射STZ（55 mg/kg ip）诱导1型糖尿病。将空腹血糖> 250 mg/dl的大鼠包括在研究中并随机分配至不同组。此后，所有组均继续该方案8个月。芹菜素（20 mg/kg）治疗减轻了糖尿病大鼠的肾功能障碍、氧化应激和纤维化（转化生长因子-β 1、纤连蛋白和IV型胶原蛋白减少）。它还显著阻止MAPK活化，从而抑制炎症（降低TNF-α、IL-6和NF-κ B表达）和凋亡（增加Bcl-2表达，降低Bax和caspase-3）。此外，组织病理学检查表明肾组织中的炎症、胶原沉积和肾小球硬化减少。此外，所有这些变化都与雷米普利产生的变化相当。因此，芹菜素通过抑制氧化应激和纤维化以及通过抑制MAPK通路来减轻DN引起的肾损伤。
Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5-20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose > 250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-beta 1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-alpha, IL-6, and NF-kappa B expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.