Inhibitory effects of ligustrazine, a modulator of thromboxane-prostacycline-nitric oxide balance, on renal injury in rats with passive Heyman nephritis.
OBJECTIVE
To explore the effects of ligustrazine on proteinuria, urinary TxB2 (metabolism of thromboxane A2, TxA2) and 6-keto-PGF1alpha (metabolism of prostacyclines I2, PG I2), glomerular inducible nitric oxide(NO) synthase (iNOS) mRNA, urinary NO3-/NO2- (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 TxB2 and 6-keto-PGF1alpha, glomerular iNOS mRNA, and urinary NO3-/NO2- 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 TxB2 in PHN rats was significantly higher than that in control rats, but the PHN rats treated with ligustrazine had significantly less proteinuria, urinary TxB2 and tissue lesions, and more urinary 6-keto-PGF(1alpha), glomerular iNOS mRNA and urinary NO2-/NO3- than the PHN rats without the administration of ligustrazine.


CONCLUSIONS
These data indicate that ligustrazine has inhibitory roles on the glomerular injury of PHN rats, which may associate with modulating the balance of TxA2-PGI2 and elevating synthesis of NO to a certain extent.
Wang
Yingwei
Y
Department of Immunology, Nanjing Medical University, Nanjing, PR China. wangyw@njmu.edu.cn
Tong
Jianxia
J
Tang
Renxian
R
Dong
Hongyan
H
Xu
Jinghua
J
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D050533:Glomerular Basement Membrane / Q000648:ultrastructure; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology* / Q000652:urine; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000209:etiology; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013928:Thromboxane A2 / Q000652:urine*
D007074:Immunoglobulin G; D009566:Nitrates; D009573:Nitrites; D011719:Pyrazines; D012333:RNA, Messenger; D009569:Nitric Oxide; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D052247:Nitric Oxide Synthase Type II; C017953:tetramethylpyrazine