Liu Kai, Xu Huiqin, Lv Gaohong, Liu Bin, Lee Maxwell Kim Kit, Lu Chunhong, Lv Xing, Wu Yunhao
National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Life Sci. 2015 Feb 15;123:78-85. doi: 10.1016/j.lfs.2014.12.028. Epub 2015 Jan 23.
Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo.
We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined.
The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney.
Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy.
糖尿病肾病是糖尿病患者终末期肾病最常见的病因。晚期糖基化终产物（AGEs）在糖尿病肾病的发展中起重要作用。我们在此评估了马钱子苷对糖尿病肾病的体内作用。
我们通过链脲佐菌素诱导C57BL/6J小鼠患糖尿病，并喂食富含AGEs的饮食，建立了糖尿病肾病模型。评估了糖尿病症状、肾功能以及胰腺和肾脏的病理组织学。测定了AGE-RAGE途径和氧化应激参数。
在实验过程中，模型小鼠表现出糖尿病的典型症状，包括体重减轻、多饮、多食、多尿、血糖水平升高和血清胰岛素水平降低。然而，0.02和0.1g/kg剂量的马钱子苷有效改善了这些糖尿病症状。与阳性对照相比，马钱子苷不同程度地降低了糖尿病小鼠的肾重/体重比、24小时尿蛋白水平以及血清尿素氮和肌酐水平。此外，马钱子苷改善了胰腺和肾脏的组织学，并减轻了肾皮质内皮细胞、系膜细胞和足细胞的结构改变。最后，我们发现马钱子苷降低了糖尿病小鼠血清和肾脏中的AGE水平，并下调了肾脏中AGE受体的mRNA和蛋白表达。马钱子苷还降低了血清和肾脏中丙二醛的水平，并提高了超氧化物歧化酶的水平。
马钱子苷通过抑制AGE途径改善了体内糖尿病肾病，可能是治疗糖尿病肾病的一种有前途的药物。
