Abd El Motteleb Dalia M, Abd El Aleem Dalia I
Department of Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Clin Exp Pharmacol Physiol. 2017 Apr;44(4):509-521. doi: 10.1111/1440-1681.12729.
Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- β (TGF-β), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.
氧化应激和炎症在糖尿病肾病（DN）的发生和发展中起关键作用。本研究旨在探讨贯叶连翘（HP）对DN可能的保护作用。将大鼠分为六组：对照组，给予生理盐水；糖尿病未治疗组（DM），注射烟酰胺（NA）后给予单剂量链脲佐菌素（STZ）；格列齐特组，给予STZ、NA + 格列齐特（10 mg/kg）；DM + HP50、DM + HP100、DM + HP200组，分别给予STZ、NA和50、100、200 mg/kg的HP。格列齐特和HP每天经口灌胃给药8周。评估血清葡萄糖、胰岛素、肾功能和组织病理学图像。此外，还检测了氧化/亚硝化应激、炎性细胞因子、凋亡和纤维化标志物。糖尿病未治疗组血清葡萄糖、尿素、肌酐及白蛋白尿增加。核因子κB（NF-κB）的肾脏蛋白表达、诱导型一氧化氮合酶（iNOS）、环氧化酶II（COXII）、IV型胶原、纤连蛋白的肾脏表达升高。丙二醛（MDA）、一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、细胞间黏附分子（ICAM-1）、单核细胞趋化蛋白-1（MCP-1）、肿瘤生长因子-β（TGF-β）、半胱天冬酶-3和细胞色素c含量也随之增加，同时血清胰岛素、过氧化物酶体增殖物激活受体（PPARγ）表达、肾脏还原型谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）活性下降。格列齐特或HP治疗减轻了STZ对所测参数的有害影响。这些发现首次表明，HP可能通过降低氧化/亚硝化应激、增强抗氧化防御机制、减少炎性细胞因子、抗纤维化、抗凋亡及降低血糖特性而对DN具有肾脏保护作用。
