Abstract: Objective To observe the effect of Tripterygium glycosides (TG) on the expression of hypoxia-inducible factor-1α
and endothelin-1 in the kidney of diabetic rats and explore the possible mechanism underlying the protective effect of TG
against diabetic nephropathy. Method Sixty 8-week-old male SD rats were randomly divided into normal control group (n=10)
and streptozotocin-induced diabetes mellitus (DM) model group (n=50). The diabetic model rats were then randomly divided
into DM group, low-dose (8 mg/kg) and high-dose (16 mg/kg) TG treatment groups, and Irbesartan (50 mg/kg) treatment
group. After 8 weeks, the levels of blood glucose (BG), 24-h urine protein (24 h Upro), serum creatinine (Scr) and blood urea
nitrogen (BUN) were measured. The pathological changes in the renal tissues were examined by optical microscopy, and the
mean glomerular area (MGA) and mean glomerular volume (MGV) were measured with pathological image analysis.
Immunohistochemical and Western blotting were used to detect the expression of HIF-1α and ET-1 protein in the renal tissue,
and their mRNA expressions were detected using real-time fluorescence quantitative PCR. Results HIF-1α and ET-1
expression increased in the kidney of diabetic rats. Compared with the diabetic model rats, the rats receiving TG and
Irbesartan treatment showed decreased levels of Scr, BUN, 24h Upro, MGA and MGV, improved renal histopathology, and
reduced expression of HIF-1α and ET-1 mRNA and protein in the renal tissue. These changes were more obvious in high-dose
TG treatment group. Correlation analysis showed that the expression of HIF-1α was positively correlated with that of ET-1,
and they were both positively correlated with kidney weight index (KW/BW), 24 h Upro, MGA, and MGV. Conclusion HIF-1α
and ET-1 are overexpressed in the kidney of diabetic rats. TG can improve kidney damage in diabetic rats and delay the
development of diabetic nephropathy by inhibiting the HIF-1α and ET-1 expression.