INCREASED
EXPRESSION OF LAMININ INDUCED BY A HIGH-LIPID DIET IN ADRIAMYCIN-INDUCED
NEPHROTIC SYNDROME
Song HM 1, Wei M 1, Li XW 2, Duan L 2,
Zhu CY 1
1 Department of Pediatrics, 2 Department
of Nephrology, Peking Union Medical College (PUMC) Hospital, Beijing, China
Objective: To determine the effect of
hypercholesterolemia induced by high-lipid diet on the expression of
laminin (LN), which is a ubiquitous and major component and play key
structural and functional role in tubular basement membrane (TBM).
Methods: A single injection of adraimycin (ADR)
5mg/kg body weight via vein was administrated in the nephrotic syndrome
(NS) group (n=20). Non-NS rats (n=20) received only the vehicle. The
animals in NS and non-NS groups were subdivided into standard chow group
and lipid-rich group. Serum cholesterol and urinary protein excretion were
assayed; immunohistochemistry and slot blotting were used to determine the
expression of LN in adriamycin-induced nephritic syndrome (NS) and non-NS
rats fed with standard chow and high-lipid chow.
Results: The results showed that serum total
cholesterol level was significantly higher in rats with high-lipid chow in
both the non-NS rats (2.2±0.3 vs. 0.9±0.1 g/L, p<0.01) and the NS rats (9.5±0.2 vs. 2.3±0.3 g/L, p<0.01). The urinary protein
excretion was significantly increased in the high-lipid diet rats than that
in standard chow rats (76.2±24.2 vs. 44.8±13.6 mg/24h, p<0.05) in NS rats. The immunohistochemical assay
showed that the production of LN was increased in the NS group, especial in
the rats with high-lipid chow. The increased mRNA expression of LN B2
chain was also detected with slot blotting in both the NS (2.4±0.4 vs.1.5±0.3, p<0.001) and the non-NS rats with
high-lipid chow (0.8±0.2 vs. 0.3±0.1, p<0.01), and it was more obvious in the rats with NS.
Conclusion: Our findings indicated that diet-induced
hypercholesterolemia could lead to over-production of LN in TBM, especially
in the rats with an adriamycin-induced nephrosis, suggesting that
hyperlipidemia may also aggravate tubulointerstitial lesions in nephritic
rats.