Department of Nephrology, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Am J Chin Med. 2012;40(3):521-36. doi: 10.1142/S0192415X12500401.
Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall., which has shown renoprotection in experimental diabetic nephropathy. Activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage. Macrophages also play an essential role in the pathogenesis of diabetic nephropathy. Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. TGP (50, 100, and 200 mg/kg) was administered orally once a day for eight weeks. Levels of p-JAK2 and p-STAT3 were determined by Western blot analysis. Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. The elevated 24-h urinary albumin excretion rate was markedly attenuated by treatment with 50, 100, and 200 mg/kg TGP. Western blot analysis showed that the significantly increased levels of p-JAK2, p-STAT3 proteins in the kidneys of diabetic rats were significantly inhibited by 50, 100, and 200 mg/kg TGP treatment. The marked accumulation and proliferation of macrophages in diabetic kidneys were significantly inhibited by TGP treatment. ED-1+/p-STAT3+ cells were significantly increased in the kidneys from the model group but were significantly inhibited by TGP treatment. These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action.
白芍总苷（TGP）是白芍的主要活性成分，已在实验性糖尿病肾病中显示出肾脏保护作用。Janus 激酶/信号转导和转录激活因子（JAK/STAT）的激活是高血糖导致肾脏损伤的重要机制。巨噬细胞在糖尿病肾病的发病机制中也起着至关重要的作用。在此，我们研究了 TGP 调节链脲佐菌素（STZ）诱导的糖尿病大鼠 JAK2/STAT3 激活和巨噬细胞增殖的能力。TGP（50、100 和 200mg/kg）每天口服一次，连续八周。通过 Western blot 分析测定 p-JAK2 和 p-STAT3 的水平。免疫组织化学和双重免疫组织化学用于鉴定 p-STAT3、ED-1、PCNA/ED-1 和 p-STAT3/ED-1 阳性（+）细胞。用 50、100 和 200mg/kg TGP 治疗可显著减轻 24 小时尿白蛋白排泄率的升高。Western blot 分析表明，TGP 治疗可显著抑制糖尿病大鼠肾脏中 p-JAK2、p-STAT3 蛋白水平的显著升高。TGP 治疗可显著抑制糖尿病肾脏中巨噬细胞的明显积聚和增殖。模型组肾脏中 ED-1+/p-STAT3+细胞明显增加，但 TGP 治疗可明显抑制。这些结果表明 TGP 可显著抑制糖尿病肾病的进展，并提示这些保护作用与 TGP 抑制 JAK2/STAT3 途径和巨噬细胞增殖和作用的能力有关。
