Department of Nephrology, Shandong University Qi Lu Hospital Qing‑Dao, Qingdao, Shandong 266000, P.R. China.
Department of Nephrology, Shandong University Qi Lu Hospital, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2018 Aug;18(2):1447-1454. doi: 10.3892/mmr.2018.9140. Epub 2018 Jun 6.
Diabetic nephropathy (DN) is by far the most common cause of end‑stage renal disease (ESRD) in industrial countries, accounting for ~45% of all new ESRD cases in the United States. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants, with an antioxidant ability 50‑fold greater than that of vitamin E and 20‑fold greater than that of vitamin C. The present study investigated whether GSPE can protect against streptozotocin (STZ)‑induced DN and aimed to elucidate a possible mechanism. Male Sprague Dawley rats were randomly divided into three groups: Control group (N), diabetes mellitus group (DM) injected with 40 mg/kg STZ, and the GSPE treatment group (intragastric administration of 250 mg/kg/day GSPE for 16 weeks after diabetes was induced in the rats). Blood and kidney samples were collected after treatment. The renal pathological changes were determined with periodic acid‑Schiff (PAS) staining, while the protein expression levels of glucose‑regulated protein 78 (GRP78), phosphorylated‑extracellular signal‑regulated kinase (p‑ERK) and Caspase‑12 were determined by western blotting and immunohistochemical staining. Apoptosis was determined with a terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL) assay. Compared with the DM group, the GSPE group had no significant changes in the blood urea nitrogen (BUN) level and serum creatinine (Scr) level, but showed a significant decline in the renal index (RI) level and 24‑h urinary albumin level (P<0.05). The histopathology results indicated very little pathological damage in the GSPE group. Compared with the DM group, the GSPE group had a significantly reduced number of TUNEL‑positive cells (P<0.05), and the GSPE group had an obvious reduction in the protein expression of GRP78, p‑ERK, and Caspase‑12 (P<0.05). In this study, the results indicated that GSPE can protect renal function and attenuate endoplasmic reticulum stress‑induced apoptosis via the Caspase‑12 pathway in STZ‑induced DN.
糖尿病肾病（DN）是目前工业化国家终末期肾病（ESRD）最常见的原因，约占美国所有新 ESRD 病例的 45%。葡萄籽原花青素提取物（GSPE）是一种强大的抗氧化剂，其抗氧化能力是维生素 E 的 50 倍，维生素 C 的 20 倍。本研究旨在探讨 GSPE 是否能防治链脲佐菌素（STZ）诱导的糖尿病肾病，并旨在阐明其可能的机制。雄性 Sprague Dawley 大鼠随机分为三组：对照组（N）、糖尿病组（DM，大鼠注射 40mg/kg STZ）和 GSPE 治疗组（大鼠诱导糖尿病后，每天灌胃 250mg/kg GSPE 16 周）。治疗后收集血液和肾脏样本。采用过碘酸-Schiff（PAS）染色法观察肾脏病理变化，采用 Western blot 和免疫组化染色法检测葡萄糖调节蛋白 78（GRP78）、磷酸化细胞外信号调节激酶（p-ERK）和 Caspase-12 的蛋白表达水平，采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）法检测细胞凋亡。与 DM 组相比，GSPE 组的血尿素氮（BUN）和血清肌酐（Scr）水平无明显变化，但肾指数（RI）和 24h 尿白蛋白水平明显下降（P<0.05）。组织病理学结果表明，GSPE 组的病理损伤较小。与 DM 组相比，GSPE 组 TUNEL 阳性细胞数明显减少（P<0.05），GSPE 组 GRP78、p-ERK 和 Caspase-12 蛋白表达明显减少（P<0.05）。本研究表明，GSPE 通过 Caspase-12 途径减轻内质网应激诱导的细胞凋亡，从而保护 STZ 诱导的糖尿病肾病大鼠的肾功能。
