Triptolide Improves Diabetic Nephropathy by Regulating Th Cell Balance and Macrophage Infiltration in Rat Models of Diabetic Nephropathy.

OBJECTIVE

To investigate the therapeutic effect of triptolide (TP) on diabetic nephropathy (DN) in addition to its influence on helper T lymphocytes (Th) cells and monocytes/macrophages in rat models of DN.

METHODS

Diabetes was induced in rats by feeding them high-fat diets and administering low-dose streptozotocin (STZ); subsequently, they were treated with TP (6, 12, or 24 mg/kg/day respectively) for 4 weeks. The general characteristics of the rats and their kidney weight to body weight ratio were observed. Liver and kidney function tests, routine blood tests, and 24 h urine protein tests were performed. Histological and ultrastructural pathologic changes in the kidneys were examined. Changes in the proportion of Th1/Th2 cells in peripheral blood and CD4(+) T cells were measured. The serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10 were determined and the expression of these 4 cytokines in the kidneys was measured. Expression of the CD68 macrophage surface marker as well as that of phospho-nuclear factor kappa B (p-NF-κB), NF-κB, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, fibronectin (FN), IL-12, and signal transducer and activator of transcription-4 (STAT4) was evaluated in the kidneys.

RESULTS

Elevated urine micro-albumin (UMA) and renal histological and ultrastructural changes were observed after the induction of diabetes. DN was associated with delayed immune-inflammatory responses induced by up-regulation of the proportion of Th1 cells and increase of the pro-inflammatory cytokines IFN-γ and TNF-α secreted by Th1 cells. In addition, down-regulation of the proportion of Th2 cells and decrease of the anti-inflammatory cytokines IL-4 and IL-10 secreted by Th2 cells were observed. TP could improve DN by regulating the Th1/Th2 cell balance. Macrophage infiltration as well as expression of inflammatory and pro-fibrogenic factors significantly increased in the kidneys of diabetic rats, which were suppressed by TP with the improvement in the medium-dose TP group (12 mg/kg/d) being the most significant.

CONCLUSION

TP can improve DN by regulating the Th1/Th2 cell balance and by reducing macrophage infiltration as well as the expression of relevant inflammatory factors in the kidney.