Inhibitory Effects of Ligustrazine, a Modulator of Thromboxane-Prostacycline-Nitric Oxide Balance, on Renal Injury in Rats with Passive Heyman Nephritis

摘要

Aims: To explore the effects of ligustrazine on protein-uria, urinary TxB_2 (metabolism of thromboxane A_2, TxA_2) and 6-keto-PGF_(1alpha)(metabolism of prostacyclines l_2, PG l_2), glomerular inducible nitric oxide(NO) synthase (iNOS) mRNA, urinary NO_3~-/NO_2~- (decomposing products of NO) and pathological changes in rats with passive Heymann nephritis (PHN). Methods: A rat PHN model was induced by intravenous injection of rabbit anti-rat renal tubular antigen (Tub-Ag) antiserum, and ligustrazine was given intraperitoneally into PHN rats every 2 days for 1-5 weeks. Then, proteinuria, urinary TxB_2 and 6-keto-PGF_(1alpha), glomerular iNOS mRNA, and urinary NO_3~-/NO_2~- were measured by sulfosalicylic acid, radioimmunoassay (RIA), Northern blot and nitric acid reductase methods, respectively. Moreover, the damage to the renal tissue of the rats was observed under light and electron microscopy and immunofluorescence (IF). Results: The urinary TxB_2 in PHN rats was significantly higher than that in control rats, but the PHN rats treated with ligustrazine had significantly less proteinuria, urinary TxB_2 and tissue lesions, and more urinary 6-keto-PGF_(1alpha), glomerular iNOS mRNA and urinary NO_2~-/NO_3~- than the PHN rats without the administration of ligustrazine. Conclusion: These data indicate that ligustrazine has inhibitory roles on the glomerular injury of PHN rats, which may associate with modulating the balance of TxA_2-PGI_2 and elevating synthesis of NO to a certain extent.