甜菜碱对db/db小鼠糖尿病肾病损伤的作用

Effects of Betaine on Diabetic Nephropathy in db/db Mice

摘要:

为探究甜菜碱对db/db小鼠糖尿病肾病损伤的保护作用，将7月龄db/db小鼠随机分为模型组（生理盐水），阳性对照组（脂必妥），甜菜碱低剂量组（200 mg/kg）、中剂量组（400 mg/kg）、高剂量组（800 mg/kg）。所有小鼠均饲以高脂饲料，以诱发糖尿病肾病（DN）模型。以甜菜碱连续灌胃6周后，进行肾组织病理学观察，并检测小鼠体重，血清中血尿素氮（BUN）、血糖（GLU），总胆固醇（TC），甘油三酯（TG）、低密度脂蛋白（LDL）、转化生长因子-β1（TGF-β1）与肿瘤坏死因子-α（TNF-α）的水平。结果显示，甜菜碱处理组与模型组相比，肾小球基底膜无明显增厚，细胞外基质、糖原物质沉积及纤维含量减少，蛋白管型和炎性细胞浸润基本消失，肾小管结构逐渐恢复正常，体重和BUN、GLU、TC、TG、LDL、TNF-α、TGF-β1水平均显著降低（P<0.05），最高分别降低11.5 g、3.0 mM、5.3 mM、3.1 mM、0.42 mM、0.64 mM、21 ng/L、30 ng/L。表明甜菜碱对db/db小鼠具有降糖、降脂、改善肾功能的生理作用，能延缓或抑制糖尿病肾病微血管炎症过程。

Abstract:

To evaluate the protective effects of betaine on diabetic nephropathy (DN) in db/db mice, 7 months old db/db mice were randomly divided into negative control group (physiological saline), positive control group (Zhibituo), low (200 mg/kg), middle (400 mg/kg) and high dose (800 mg/kg) betaine group. The mice were fed by high-fat diet to induce DN. After being intragastric administrated by betaines for 6 weeks, the kidney paraffin sections were prepared and the pathological changes were analyzed based on staining, the body weight and BUN, GLU, TC, TG, LDL, TNF-α, TGF-β1 level were also investigated. The results showed that the glomerular basement membrane in the betaine and Zhibituo treatment group did not thicken; extracellular matrix, the glycogen material deposition and fiber content reduced; protein casts and inflammatory cell infiltration disappeared. Furthermore, the structure of renal tubule gradually returned to normal; the body weight and BUN, GLU, TG, TC, LDL, TNF-α, TGF-β1 level were significantly decreased (P < 0.05) by 11.5 g, 3.0 mM, 5.3 mM, 3.1 mM, 0.42 mM, 0.64 mM, 21 ng/L and 30 ng/L, respectively. It can be speculated that betaine has a hypoglycemic activity, lipid-lowering effect, and protective effect on the kidney injury of db/db mice. It may delay or inhibit the inflammatory process of the capillary vessel in diabetic nephropathy.