Grape seed proanthocyanidins protect against streptozotocin‑induced diabetic nephropathy by attenuating endoplasmic reticulum stress‑induced apoptosis.
Grape seed proanthocyanidins protect against streptozotocin‑induced diabetic nephropathy by attenuating endoplasmic reticulum stress‑induced apoptosis.
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DOI：
10.3892/mmr.2018.9140
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Gao Z;Liu G;Hu Z;Shi W;Chen B;Zou P;Li X
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，占美国所有新发ESRD病例的约45%。葡萄籽原花青素提取物（GSPE）是强大的抗氧化剂，其抗氧化能力是维生素E的50倍，是维生素C的20倍。本研究旨在探讨GSPE对链脲佐菌素（STZ）诱导的DN的保护作用及其可能的机制。将雄性SD道利大鼠随机分为3组：对照组（N）、糖尿病组（DM）和GSPE治疗组（GSPE 250 mg/kg/d，连续灌胃16周）。给药后采集血液和肾脏样本。PAS染色观察肾脏病理改变，Western blotting和免疫组织化学染色检测葡萄糖调节蛋白78（GRP 78）、磷酸化细胞外信号调节激酶（p-ERK）和Caspase-12蛋白表达水平。用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法测定细胞凋亡。与DM组比较，GSPE组血尿素氮（BUN）、血肌酐（Scr）水平无明显变化，肾指数（RI）、24 h尿白蛋白水平明显下降（P<0.05）。组织病理学结果表明GSPE组的病理损伤很小。与DM组相比，GSPE组TUNEL阳性细胞数明显减少（P<0.05），GRP 78、p-ERK、Caspase-12蛋白表达明显减少（P<0.05）。本研究结果提示，GSPE可通过Caspase-12途径保护STZ诱导的DN大鼠肾功能，减轻内质网应激诱导的细胞凋亡。
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.
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影响因子：
19.6
作者：
Ohse, T.;Inagi, R.;Nangaku, M.
通讯作者：
Nangaku, M.
影响因子：
--
作者：
Li, Xianhua;Xiao, Yunling;Ma, Yabing
通讯作者：
Ma, Yabing
DOI：
10.1016/j.bbrc.2008.04.031
发表时间：
2008-06-13
影响因子：
3.1
作者：
Liu, Guanghui;Sun, Yingying;Ge, Zhiming
通讯作者：
Ge, Zhiming
影响因子：
3.8
作者：
Luo, Zhi-Feng;Feng, Bing;Yuan, Fa-Huan
通讯作者：
Yuan, Fa-Huan
影响因子：
3.6
作者：
Song, Y;Li, C;Cai, L
通讯作者：
Cai, L