Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
Int J Biol Macromol. 2017 Dec;105(Pt 3):1587-1594. doi: 10.1016/j.ijbiomac.2017.03.124. Epub 2017 Mar 27.
Diabetic nephropathy (DN) is one of the most severe diabetic complication and it is becoming become a worldwide epidemic, accounting for approximately one-third of all case of end-stage renal disease. However, the underlying mechanism and strategy to alleviate renal injury remain unclear. In the present study, we assessed the protective effect of bamboo leaf extract on the DN, and investigated the underlying mechanism by which bamboo leaf extract ameliorating DN. Diabetic rats were induced by 4 weeks high sugar and high fat diet, and then injected a single dose of STZ (35mg/kg) into abdominal cavity. Different dose of bamboo extract (50mg/kg, 100mg/kg and 200mg/kg) were orally administered every day for a period of 12 weeks. Body weight, blood glucose, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and 24-hour urinary protein (24 h-UP) were assessed. Total superoxide dismutase (T-SOD) activity and MDA (methane dicarboxylic aldehyde, MDA) level were tested by assay kit. Microstructural changes were observed by hematoxylin-eosin (HE) staining and electron microscopy. Expression of phosphorylated ser/thr protein kinase (P-AKT), phosphorylated glycogen synthase kinase-3 beta (P-GSK-3β), B cell lymphoma/leukemia 2-associated X protein (BAX) and cleaved-cysteinyl aspartate-specific proteinase-3 (Cleaved Caspase-3) were measured by Western-Blotting (WB). Results showed that diabetic rats had weight loss, high blood glucose, HbAlc, BUN, Scr and 24-UP and T-SOD activity were increased and MDA level was decreased in diabetic rats. Moreover, hyperglycemia could injury renal tissue ultrastructure, inhibit P-AKT level and increase P-GSK-3β, BAX and Cleaved Caspase-3 levels in rats. However, bamboo leaf extract treatment could reduce body weight loss, BUN, Scr, 24 h-UP and MDA level, improve T-SOD activity and alleviate renal injury in diabetic rats. Furthermore, bamboo leaf extract increased P-AKT level, decreased P-GSK-3β, BAX and Cleaved Caspase-3 levels in STZ-diabetic rats. In conclusion, our study suggested that bamboo leaf extract ameliorated DN in diabetic rats, and this protective effect is possibly related to suppressing oxidative stress through activating AKT signaling pathway. Bamboo leaf extract treatment may be a potential promising therapy for DN.
糖尿病肾病(DN)是最严重的糖尿病并发症之一,已成为全球性疾病,约占所有终末期肾病病例的三分之一。然而,其肾脏损伤的潜在机制和缓解策略仍不清楚。在本研究中,我们评估了竹叶提取物对 DN 的保护作用,并通过研究竹叶提取物改善 DN 的作用机制来探讨其潜在机制。通过 4 周高糖高脂饮食诱导糖尿病大鼠,然后向腹腔内单次注射 STZ(35mg/kg)。每天口服不同剂量的竹叶提取物(50mg/kg、100mg/kg 和 200mg/kg),持续 12 周。评估体重、血糖、糖化血红蛋白 A1c(HbAlc)、血尿素氮(BUN)、血清肌酐(Scr)和 24 小时尿蛋白(24 h-UP)。通过试剂盒测定总超氧化物歧化酶(T-SOD)活性和丙二醛(MDA)水平。苏木精-伊红(HE)染色和电子显微镜观察微观结构变化。通过 Western-Blotting(WB)测定磷酸化丝氨酸/苏氨酸蛋白激酶(P-AKT)、磷酸化糖原合酶激酶-3β(P-GSK-3β)、B 细胞淋巴瘤/白血病 2 相关 X 蛋白(BAX)和半胱氨酸天冬氨酸特异性蛋白酶-3(Cleaved Caspase-3)的表达。结果表明,糖尿病大鼠体重减轻,血糖、HbAlc、BUN、Scr 和 24-UP 升高,T-SOD 活性升高,MDA 水平降低。此外,高血糖可损伤肾脏组织超微结构,抑制大鼠 P-AKT 水平,增加 P-GSK-3β、BAX 和 Cleaved Caspase-3 水平。然而,竹叶提取物治疗可减少糖尿病大鼠体重减轻、BUN、Scr、24 h-UP 和 MDA 水平,提高 T-SOD 活性,减轻糖尿病大鼠肾脏损伤。此外,竹叶提取物增加了 STZ 糖尿病大鼠的 P-AKT 水平,降低了 P-GSK-3β、BAX 和 Cleaved Caspase-3 水平。综上所述,本研究表明竹叶提取物改善了糖尿病大鼠的 DN,这种保护作用可能与通过激活 AKT 信号通路抑制氧化应激有关。竹叶提取物治疗可能是一种有前途的 DN 治疗方法。