目的 通过构建糖尿病肾病（DN）大鼠模型，研究环孢素A对DN大鼠足细胞氧化应激损伤的影响。方法 将30只SPF级SD大鼠随机分为对照组、模型组和环孢素A组，每组10只。通过高糖高脂饲料联合链脲佐菌素（STZ）建造大鼠DN大鼠模型（ip 40 mg/kg 1%链脲佐菌素）。建模4周后，环孢素A组大鼠ig 3 mg/kg环孢素A，1次/d，连续给药4周，其余两组ig等量饮用水。记录大鼠体质量，尿蛋白测定试剂盒检测24 h尿蛋白，全自动血糖仪检测空腹血糖（FBG）；AU480全自动生化分析仪检测血肌酐（Scr）和尿素氮（BUN）；化学荧光法检测活性氧（ROS）；化学比色法检测过氧化物歧化酶（SOD）活性；硫代巴比妥酸比色法检测丙二醛（MDA）水平；Western blotting检测肾组织nephrin、p38 MAPK和p-p38 MAPK蛋白表达水平。结果 与对照组相比，模型组大鼠体质量明显减轻，24 h尿蛋白、FBG、Scr、BUN、ROS水平和MDA含量显著增加，nephrin、p38 MAPK和p-p38 MAPK蛋白表达显著增加，而SOD活性明显降低（P＜0.05、0.01）。与模型组相比，环孢素A组大鼠体质量显著增加，24 h尿蛋白、Scr、BUN、ROS水平及MDA含量显著降低，nephrin、p38 MAPK和p-p38 MAPK蛋白表达显著降低，而SOD活性明显升高（P＜0.05、0.01）。结论 环孢素A可能通过调控p38 MAPK信号通路抑制氧化应激，改善DN大鼠肾组织足细胞损伤，缓解DN大鼠病情进展。

Objective To study the effect of cyclosporine A on oxidative stress injury of podocytes in a diabetic nephropathy (DN) rats model.Methods 30 SPF SD rats (10 rats in each group) were randomly divided into control group, model group and cyclosporine A group. The rat model of diabetic nephropathy was established by high-sugar and high-fat diet combined with streptozotocin (STZ) (40 mg/kg ip 1% streptozotocin). After 4 weeks of modeling, the rats in cyclosporine A group were intragastrically administered with cyclosporine A of 3 mg/kg, once daily for 4 weeks, and the other two groups were given the same amount of drinking water. The body mass of rats was recorded, 24 h urinary protein, fasting blood glucose (FBG), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by urine protein determination Kit, automatic blood glucose analyzer, reactive oxygen species (ROS) were detected by chemical fluorescence method, superoxide dismutase (SOD) was detected by chemical colorimetry, malondialdehyde (MDA) was detected by thiobarbituric acid colorimetry, and renal protein expression levels of nephrin, p38 MAPK and p-p38 MAPK were detected by Western blot.Results Compared with the control group, the body weight of the model group was significantly lighter, the levels of 24 h urinary protein, FBG, Scr, BUN, ROS and MDA were significantly increased, and the protein expressions of nephrin, p38 MAPK and p-p38 MAPK were significantly increased, while the activity of SOD was significantly decreased (P < 0.05 and 0.01). Compared with the model group, the body weight of cyclosporine A group significantly increased, the levels of 24 h urinary protein, Scr, BUN, ROS, and MDA were significantly decreased, the expression of nephrin, p38MAPK, and p-p38MAPK protein were significantly decreased, while the activity of SOD were significantly increased in cyclosporine A group (P < 0.05, 0.01).Conclusion Cyclosporine A may inhibit oxidative stress by regulating p38MAPK signaling pathway, improve podocyte injury in renal tissue of DN rats and alleviate the disease progression of DN rats.

R965

西安市卫生健康委员会科研一般研究项目（2020yb12）