糖尿病肾病大鼠动物模型建立及INF-α干预机制研究

Establishment of Animal Model of Diabetic Nephropathy Rats and Study of INF-α Intervention Mechanism

目的探讨糖尿病肾病大鼠动物模型建立及TNF-α干预机制。方法选择SD大鼠60只作为对象,随机数字法分为对照组和观察组,各30只。对照组大鼠腹腔注射柠檬酸缓冲液,观察组在对照组基础上采用高糖高脂饲料联合5%葡萄糖饮水喂养,诱导胰岛素抵抗,2周后腹腔注射STZ,连续注射3 d,诱发持续高糖血症。采用酶联免疫吸附法在建模前、建模2周、建模4周检测观察组大鼠血糖、尿白蛋白、肌酐水平,同时检测两组大鼠TNF-α水平,分析糖尿病动物模型建立及TNF-α干预机制。结果①对照组大鼠全身状态良好,体质量增加,皮毛光滑亮泽,观察组大鼠建模成功后出现多食、多饮、多尿及生长迟缓现象,成模4周后体重低于对照组,差异有统计学意义(P<0.05);②观察组建模2周血糖水平(8.21±0.21)mmol/L,建模4周血糖水平(31.21±1.04)mmol/L,均高于对照组的(6.32±0.19)mmol/L、(6.74±0.24)mmol/L),差异有统计学意义(P<0.05);③观察组建模2周TNF-α水平为(3.03±0.23)mmol/L,建模4周TNF-α水平为(12.10±1.12)mmol/L,均高于对照组的(1.64±0.58)mmol/L、(1.69±0.62)mmol/L,差异有统计学意义(P<0.05)。结论高糖高脂饲料联合浓度为5%葡萄糖饮水配合小剂量STZ能建立理想的糖尿病肾病大鼠动物模型,可以明确糖尿病肾病发展伴有TNF-α炎症因子水平升高,进一步为TNF-α干预机制研究奠定了基础。

Objective To investigate the establishment of animal models of diabetic nephropathy rats and the mechanism of TNF-a intervention.Methods 60 SD rats were selected as the subjects.The random number method was divided into control group and observation group,30 each.Rats in the control group were intraperitoneally injected with citrate buffer.The observation group was fed with high-sugar and high-fat diet combined with 5%dextrose water to induce insulin resistance.After 2 weeks,STZ was injected intraperitoneally for 3 consecutive days,induced persistent hyperglycemia.The levels of blood glucose,urinary albumin and creatinine in the observation group were measured by enzyme-linked immunosorbent assay(ELISA)before modeling,2 weeks of modeling,and 4 weeks of modeling.The levels of TNF-αin the two groups were also measured and TNF-a intervention mechanism.Results①The rats in the control group had good systemic condition,the body mass increased,and the fur was smooth and shiny.The rats in the observation group showed polyphagia,polydipsia,polyuria and growth retardation after successful modeling.After 4 weeks of modeling,the body weight was lower than that of the control group,the difference was statistically significant(P<0.05);②The observation group modeling 2 weeks blood glucose level(8.21±0.21)mmol/L,modeling 4 weeks blood glucose level(31.21±1.04)mmol/L,they were higher than the control group(6.32±0.19)mmol/L,(6.74±0.24)mmol/L,the difference was statistically significant(P<0.05);③The level of TNF-αin the observation group was(3.03±0.23)mmol/L for 2 weeks,and the level of TNF-αwas(12.10±1.12)mmol/L for 4 weeks,which was higher than that of the control group(1.64±0.58)mmol/L,(1.69±0.62)mmol/L,the difference was statistically significant(P<0.05).Conclusion The high concentration of high-fat and high-fat diet combined with 5%dextrose drinking water combined with low-dose STZ can establish an ideal animal model of diabetic nephropathy in rats.It can be confirmed that the development of diabetic nephropathy is accompanied by elevated levels of TNF-a inflammatory factors,and further intervention for TNF-α.Mechanism research laid the foundation.