Abstract:

AIM: To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP) on streptozocin(STZ)-induced-nephropathy in type 2 diabetic rats.  METHODS: Fifty SD rats were randomly divided into control group (n=10) and model group (n=40). All model rats were fed with high-fat diet for 4 weeks and then injected with streptozotocin (STZ, 40 mg/kg, ip). Fasting blood glucose (FBG) was measured by One-Touch glucometer after 72 h. Rats with fasting blood glucose above 16.67 mmol/L were then randomly divided into four groups: model, metformin (250 mg/kg), low-TMP (80 mg/kg) and high-TMP (160 mg/kg) groups, and the later three received respective drug for 8 weeks, while control and model groups were given equal amount of distilled water by intragastric administration. At the end of the experiment, blood glucose, urine protein, blood urea nitrogen, creatinine, insulin, HOMA-IRI and receptor for advanced glycationend-products (RAGEs) were measured. The expression of high mobility group box 1 (HMGB1) in kidney tissue of rats was determined by immunohistochemistry. Pathological damages of kidney were observed under light microscope. RESULTS:After 8 weeks' administration, compared with the model group, metformin group, low-TMP and high-TMP group showed significant decrease in the dynamic fasting blood glucose (P<0.01) and urinary protein excretion of total dynamic (P<0.05 or P<0.01); Metformin and high-TMP can significantly reduce the level of Cr, BUN and RAGEs; the protein expressions of HMGB1 in metformin group and high-TMP group were significantly lower than that in model group (P<0.05); pathological damages of kidney tissue were significantly reduced.CONCLUSION: TMP exhibited protective effect on STZ induced nephropathy in type 2 diabetic rats and its mechanism may be related to the down-regulation of HGMB1 expression and reducing contents of RAGEs.

Key words:  tetramethylpyrazine, diabetic nephropathy, HMGB1, RAGEs