| [Background/Aims] The study is made up of 2 parts. In the first part, the authors reviewed the pathomechanisms of podocyte injury and the effects of Chinese herbal medicine (CHM) on podocyte injury under the condition of diabetic nephropathy (DN). The pathological characters of podocyte injury in DN mainly refer to the change of podocyte structure and function, including foot process effacement, reduction of podocyte number and density, podocyte apoptosis, podocyte epithelial-mesenchymal transdifferentiation (EMT) and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney, such as mammalian target of rapamycin (mTOR) pathway, transforming growth factor (TGF)-β1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN, some CHM extracts, such as multiglycoside of Tripterygium wilfordii Hook.f. (GTW), triptolide (TP), astragaloside IV (AS-IV), astragalus polysaccharide (APS) and panax notoginseng saponins (PNS), have the protective effects in vivo or in vitro. In the second part, as the focus of this study, using the DN model rats, the authors clarified the effects and mechanisms of GTW improving podocyte injury in vivo.[Methods] The DN model rats were induced by unilateral nephrectomy and intraperitoneal injection of streptozotocin (STZ). The 20 rats were randomly divided into 4 groups, the normal group, the model group, the GTW group and the Rapamycin group (5 rats for each group). After establishing the DN model rats successfully, the rats in each group were daily oral administrated with distilled water (2 mL) or GTW suspension (50 mg·kg-1·d-1) or Rapamycin suspension (1 mg·kg-1·d-1) respectively for 4 weeks. After the drug administration for 4 weeks, all rats were sacrificed. During the experiment, general condition, body weight (BW) and blood glucose (BG) of each rat were monitored every week respectively; Urine and urinary albumin (UAIb) of each rat were collected and detected respectively every 2 weeks; After all rats were sacrificed, blood and kidneys were collected, and then kidney weight (KW), kidney hypertrophy index (KHI) and serum biochemical indicators were observed respectively; In addition, glomerular morphology and ultrastructure, the protein expressions of podocyte structural molecules and the key signaling molecules in mTORCl pathways in the kidney were analyzed respectively.[Results] Compared with the DN model rats, both GTW and Rapamycin could improve kidney appearance, KHI and glomerular morphology; Both of them could reduce UAlb, and that, GTW could ameliorate serum albumin (Alb); Both of them could improve podocyte form, and GTW could up-regulate the protein expressions of podocin and CD2AP, while Rapamycin could only up-regulate the protein expression of podocin; Both of them had no effects on the protein expressions of nephrin and nephl, but could increase the level of combination between nephrin and nephl; Both of them could improve the protein expressions of the key signaling molecules of mTORC1 pathways in the kidney in different extent; Nevertheless, GTW and Rapamycin had no effects on BW, BG, renal function and liver function.[Conclusions] By means of the DN model rats, the authors demonstrated that ①There are 3 pathological characters of podocyte injury in DN including foot process effacement, down-regulation of podocin and CD2AP protein expressions and disorder of combination between nephrin and nephl; ①GTW and Rapamycin can not only ameliorate podocyte injury, but also reduce the related glomerular sclerotic lesions; ③Unlike Rapamycin, GTW can not only up-regulate the protein expressions of podocin and CD2AP, but also increase the level of combination between nephrin and nephl; ④Both GTW and Rapamycin can improve podocyte injury through regulating the activities of PI3K/Akt/mTORC1 and AMPK/mTORC1 signaling pathways. |
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