Yan Ling, Xu Xiaoxiao, Fan Yanbo, Zhang Lifang, Niu Xiaojing, Hu Aimin
Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430014, China.
Department of Preventive Treatment of Disease, Wuhan No.1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430030, China.
Evid Based Complement Alternat Med. 2022 Apr 11;2022:3110854. doi: 10.1155/2022/3110854. eCollection 2022.
Traditional Chinese medicine has certain advantages in the prevention and treatment of diabetic nephropathy (DN); thus, Chinese medicine therapy is considered as a promising strategy for treating DN. Here, the diabetic nephropathy model was established and intervened with Tangshen Decoction to explore its repair effect on diabetic kidney injury and the mechanism of autophagy. Different doses (10, 20 g·kg) of Tangshen Decoction (so-called Tangshen Jian, TSJ) or metformin were used to intervene for 16 weeks. The body weight (BW) and fasting blood glucose (FBG) of rats in each group were regularly monitored; a urine protein test kit (CBB method) was used to detect changes in urine protein (UP) content. The serum biochemical indicators, including Cr (creatinine), BUN (blood urea nitrogen), TC (total cholesterol), and TG (triglyceride), were detected by an automatic biochemical analyzer. HE (hematoxylin-eosin) staining, PAS, and electron microscopy were used to observe the podocyte damage. We showed that administration of TSJ or metformin prevented the increases in FBG level, serum Cr, BUN, TC, and TG level, and urine protein excretion in diabetic nephropathy. Simultaneously, the foot process fusion and fall-off were partially reversed after TSJ treatment. TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy. Therefore, TSJ may enhance podocyte autophagy to relieve diabetic nephropathy through modulation of p-AMPK/p-ULK1 signaling, which has important application prospects in the clinical treatment of diabetic kidney damage in the future.
中医在糖尿病肾病（DN）的防治方面具有一定优势；因此，中医治疗被认为是治疗DN的一种有前景的策略。在此，建立糖尿病肾病模型并用糖肾方进行干预，以探讨其对糖尿病肾损伤的修复作用及自噬机制。使用不同剂量（10、20 g·kg）的糖肾方（即糖肾煎，TSJ）或二甲双胍进行干预16周。定期监测各组大鼠的体重（BW）和空腹血糖（FBG）；使用尿蛋白检测试剂盒（考马斯亮蓝法）检测尿蛋白（UP）含量的变化。通过自动生化分析仪检测血清生化指标，包括肌酐（Cr）、血尿素氮（BUN）、总胆固醇（TC）和甘油三酯（TG）。采用苏木精-伊红（HE）染色、PAS染色和电子显微镜观察足细胞损伤情况。我们发现，给予TSJ或二甲双胍可预防糖尿病肾病大鼠FBG水平、血清Cr、BUN、TC和TG水平以及尿蛋白排泄的升高。同时，TSJ治疗后足突融合和脱落得到部分逆转。TSJ或二甲双胍显著上调nephrin和podocin的水平，同时糖尿病肾病中足细胞自噬明显增强，p-AMPK/p-ULK1信号通路激活。因此，TSJ可能通过调节p-AMPK/p-ULK1信号通路增强足细胞自噬以缓解糖尿病肾病，这在未来糖尿病肾损伤的临床治疗中具有重要应用前景。
