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[Effect of triptolide on the expression of RANTES in the renal tissue of diabetic nephropathy rats]
Objective:
To investigate the effect of triptolide (TPL) on the renal tissue of diabetic rats and its possible mechanisms.
Methods:
SD rats were randomly divided into the normal control group (as the normal group), the diabetic model group (the model group), the low dose TPL treatment group (the low dose TPL group, TPL 0.2 mg/kg by gastrogavage), the high dose TPL treatment group (the high dose TPL group, TPL 0.4 mg/kg by gastrogavage). Equal volume of normal saline was given to rats in the normal group and the model group. Five rats were randomly selected from each group at week 4, 8, and 12 of the experiment to detect body weight, kidney weight, 24 h urinary albumin (24 h UAL), plasma glucose (FBG), total cholesterol (TC), total triglyeride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), and hemoglobin A1c (HbA1c). The mRNA and protein expression of regulated upon activation normal T-cell expressed and secreted (RANTES) in the renal tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The renal tissue was pathologically stained by HE, PAS, and Masson staining. The glomerular and renal tubular interstitial lesions were observed at each time point. The glomerular sclerosis index (GSI) was observed by PAS staining, and the renal interstitial filrosis index (RIFI) was calcutated.
Results:
Compared with the same group at week 4, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 significantly decreased in two TPL groups (P <0.01). Compared with the same group at week 8, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 also significantly decreased in the two TPL groups (P <0. 05, P <0.01). Compared with the normal group, body weight and the kidney weight obviously decreased at week 4, 8, and 12 in the model group (P <0. 01); 24 h UAL, FBG, TG, TC, HbA1c, RANTES, GSI, and RIFI were obviously elevated (P <0.01). Compared with the model group, 24 h UAL, RANTES, GSI, and RIFI also decreased in the two TPL treatment groups (P <0.01). Compared with the low dose TPL group, they were attenuated in the high dose TPL group (P <0. 05, P <0. 01).
Conclusion:
TPL could not only inhibit the over-expression of RANTES, but also improve the glomerular sclerosis and renal interstitial fibrosis in the renal tissue of diabetic rats.
Insights
Triptolide (TPL) treatment significantly reduced markers of kidney damage, including urinary albumin and RANTES, while improving glomerular sclerosis and fibrosis in diabetic rats. Higher TPL doses showed greater efficacy in protecting renal tissue.
Area of Science:
- Nephrology
- Diabetology
- Pharmacology
Background:
- Diabetic nephropathy is a major complication of diabetes, characterized by progressive kidney damage.
- Current treatments for diabetic nephropathy have limitations, highlighting the need for novel therapeutic agents.
- Triptolide (TPL), a compound derived from Tripterygium wilfordii, has shown potential anti-inflammatory and immunosuppressive properties.
Purpose of the Study:
- To investigate the therapeutic effects of Triptolide (TPL) on renal tissue in a rat model of diabetes.
- To elucidate the underlying mechanisms by which TPL exerts its protective effects on diabetic kidneys.
Main Methods:
- Streptozotocin-induced diabetic Sprague-Dawley rats were treated with varying doses of TPL (0.2 mg/kg and 0.4 mg/kg) or saline.
- Key biochemical markers (e.g., 24-hour urinary albumin, plasma glucose, HbA1c) and renal function indicators were assessed.
- Renal tissue expression of RANTES (regulated upon activation normal T-cell expressed and secreted) was measured using RT-PCR and ELISA.
- Histopathological analysis (HE, PAS, Masson staining) evaluated glomerular sclerosis and interstitial fibrosis, quantified by glomerular sclerosis index (GSI) and renal interstitial fibrosis index (RIFI).
Main Results:
- Diabetic rats exhibited significantly elevated 24-hour urinary albumin, RANTES expression, GSI, and RIFI compared to normal controls.
- TPL treatment dose-dependently reduced these markers of renal damage.
- High-dose TPL treatment demonstrated a significant attenuation of glomerular sclerosis and renal interstitial fibrosis compared to low-dose TPL.
Conclusions:
- Triptolide effectively ameliorates renal damage in diabetic rats by inhibiting RANTES over-expression.
- TPL treatment improves glomerular sclerosis and renal interstitial fibrosis, suggesting its potential as a therapeutic agent for diabetic nephropathy.
