目的 探讨糖肾平对采用腹腔注射链脲佐菌素（STZ）诱导的糖尿病肾病（DN）大鼠足细胞损害的抑制和对PI3K/AKT信号转导通路的调控作用。方法 雄性Wistar大鼠74只，从中随机选取10只作为空白对照组，剩余大鼠进行一次性腹腔注射STZ造模，造模成功并且存活的大鼠随机分为：模型组、厄贝沙坦组、糖肾平小剂量、糖肾平大剂量组。灌胃给药剂量为：厄贝沙坦组17.5 mg·kg-1，1 mL/100 g；糖肾平小剂量组0.525 g·kg-1，1 mL/100 g；糖肾平大剂量组2.1 g·kg-1，1 mL/100 g；每4周称取大鼠体质量并测定24 h尿蛋白定量，第14周股动脉取血处死大鼠，称取肾脏质量；TUNEL染色观察肾组织足细胞凋亡；免疫组化测定肾组织PI3K、AKT、Bad蛋白表达情况；RT-PCR检测大鼠肾组织PI3K、AKT、Bad、CD2AP及nephrin mRNA表达情况。结果 与正常组比较，模型组大鼠多饮、多食、多尿、形体消瘦、皮毛干枯并且动作迟缓；大鼠肾组织中足细胞数目明显减少，PI3K及AKT表达明显降低，Bad表达明显升高（P ＜ 0.01）；经过治疗后各组大鼠一般情况均有明显好转，足细胞数目较模型组明显增多；与模型组比较，厄贝沙坦组PI3K及AKT表达明显升高，Bad阳性反应物明显较少（P ＜ 0.01）；糖肾平各治疗组PI3K及AKT表达升高，而Bad阳性反应物呈剂量依赖性得明显较少，有统计学显著差异（P ＜ 0.01）。结论 糖肾平能抵抗糖尿病肾病大鼠足细胞凋亡，其作用机制与PI3K-AKT信号通路有关。
Objective To investigate the protective effect of Tangshenping on streptozotocin (STZ) induced podocyte and its regulation on PI3K/AKT signal transduction pathway in Diabetic nephropathy (DN) rats. Methods 10 out of 74 male Wistar rats of clean grade were randomly selected as the blank control group. The rest were modeled and randomly divided into a model group, an Irbesartan group, a Tangshenping low dose group and a Tangshenping high dose group. Drug was administered by gavage according to following dosage: Irbesartan group: 17.5 mg·kg-1 and 1 mL/100 g; Tangshenping low dose group: 0.525 g·kg-1, 1 mL/100 g, Tangshenping high dose group: 2.1 g·kg-1 and 1 mL/100 g. Body weight and quantitative of ptoteinuria in 24 hour were measured every 4 weeks. After 14 weeks, blood was taken from femoral artery of rats in anesthesia, and TUNEL staining was used to observe apoptosis of podocyte in renal tissue. Immunohistochemistry was used to detect the expression of PI3K, AKT and bad protein in renal tissue. RT-PCR was used to detect the expression of PI3K, AKT, Bad, CD2AP and nephrin mRNA in renal tissue of rats. Results Compared with rats in the normal control group, rats in the model group drank more, ate more, had more urine, lost body weight, demonstrated dry fur and slow movement. The number of podocytes in kidney tissue was significantly decreased, and the blood glucose and urinary microalbumin was significantly increased. The expression of PI3K and AKT significantly was lowered and the expression of Bad was significantly increased (P < 0.01). All the treatment methods could reduce blood glucose and urine microalbumin. Number of podocytes increased significantly compared with the model group. Compared with the model group, the expression of PI3K and AKT in the Irbesartan group was significantly higher (P < 0.01), and Bad positive reactants were significantly decreased (P < 0.01). The expression of PI3K and AKT increased in all Tangshenping treatment groups and Bad positive reactant decreased in a dose-dependent manner (P < 0.01).Conclusion Tangshenping can resist apoptosis of podocyte in diabetic nephropathy rats, and its mechanism is related to PI3K-AKT signal pathway.