Tea Polypeptide Ameliorates Diabetic Nephropathy through RAGE and NF-κB Signaling Pathway in Type 2 Diabetes Mice
Tea Polypeptide Ameliorates Diabetic Nephropathy through RAGE and NF-κB Signaling Pathway in Type 2 Diabetes Mice
复制标题
茶多肽通过 RAGE 和 NF-κ B 信号通路改善 2 型糖尿病小鼠的糖尿病肾病
DOI：
10.1021/acs.jafc.8b04819
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发表时间：
2018-11-14
影响因子：
6.1
通讯作者：
Sun, Shili
中科院分区：
文献类型：
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作者：
Deng, Xuming;Sun, Lingli;Sun, Shili
糖尿病肾病(DN)是2型糖尿病(T2D)的主要并发症，是糖尿病患者死亡率的关键决定因素。开发既能控制T2D又能预防糖尿病肾病发展的新型治疗药物具有重要意义。我们研究了翠玉茶多肽(TP)对糖尿病肾病的治疗作用及其分子机制。茶多酚(1000 mg/kg体重/天，P.O.)给药5周后，高脂饮食/链脲佐菌素(HFD/STZ)诱导的糖尿病小鼠(30 mg/kg bw)的空腹血糖显著降低52.04+/-9.23%。与模型组比较，茶多酚组大鼠血清胰岛素水平降低25.54+/-6.06%，HOMA-IR、HOMA-IS及血脂水平均有不同程度的恢复(p<；0.05)。在一定程度上反映肾小球滤过功能损害程度的尿总蛋白、肌酐和尿氮较模型组分别下降了34.51±2.65%、42.24±15.24%和80.30±6.01%。在机制上，TP刺激多元醇PKC-Zeta/JNK/NF-kappa B/THF-α/iNOS和AGEs/RAGE/TGF-β1通路，上调肾小球Podocin的表达，减少促炎细胞因子的释放。这些结果有力地表明了茶多酚对糖尿病肾病的治疗潜力。
Diabetic nephropathy (DN) is a major complication of type 2 diabetes (T2D), which is a key determinant of mortality in diabetic patients. Developing new therapeutic drugs which can not only control T2D but also prevent the development of DN is of great significance. We studied the therapeutic potential of Cuiyu tea polypeptides (TP), natural bioactive peptides isolated from a type of green tea, against DN and its underlying molecular mechanisms. TP (1000 mg/kg bw/day, p.o.) administration for 5 weeks significantly reduced the fasting blood glucose by 52.04 +/- 9.23% in the high fat diet/streptozocin (HFD/STZ)-induced (30 mg/kg bw) diabetic mice. Compared to the model group, the serum insulin level of the TP group was decreased by 25.54 +/- 6.06%, while at the same time, the HOMA-IR, HOMA-IS, and lipid levels showed different degrees of recovery (p < 0.05). Moreover, in TP group mice the total urinary protein, creatinine, and urine nitrogen, all which can reflect the damage degree of the glomerular filtration function to a certain extent, dramatically declined by 34.51 +/- 2.65%, 42.24 +/- 15.24%, and 80.30 +/- 6.01% compared to the model group, respectively. Mechanistically, TP stimulated the polyol PKC zeta/JNK/NF-kappa B/THF-alpha/iNOS and AGEs/RAGE/TGF-beta 1 pathways, upregulated the expression of podocin in the glomeruli, and decreased the release of pro -inflammatory cytokines. These results strongly indicate the therapeutic potential of TP against DN.