[The effect of inhibiting nuclear factor-kappa B on the diabetic nephropathy].
OBJECTIVE
To investigate the effect of inhibiting nuclear factor-kappa B (NF-kappaB) on diabetic nephropathy (DN) and mRNA expression of fibronectin (FN) in diabetic kidneys.


METHODS
Male Wistar rats were divided into 3 groups: group A (n = 11) the normal rats, group B (n = 11) the diabetic rats without any therapy, and group C (n = 9) the diabetic rats treated with pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB). At the end of 18th week, the kidneys were taken out from all the rats to measure the NF-kappaB activity by electrophoretic mobility shift assays (EMSA) and the mRNA expression of FN by reverse transcript (RT)-PCR, as well as to observe the glomerular basement membrane (GBM) thickening and mesangial matrix (MM) density (MM area/mesangial area) by electronic microscope. 24 hour urine was also collected to measure the levels of albumin (urine albumin excretion, UAE).


RESULTS
NF-kappaB activity of renal tissue in group B [(1.85 +/- 0.54) x 10(6)] was significantly higher than that in group A [(0.07 +/- 0.11) x 10(6), P < 0.01] and the activity in group C [(0.25 +/- 0.25) x 10(6)] lower than that in group B (P < 0.01). Compared with those in group A, the UAE [(2.18 +/- 1.98) mg vs (0.41 +/- 0.47) mg, P < 0.01], the GBM thickening [(531.6 +/- 107.6) nm vs (312.4 +/- 25.4) nm, P < 0.01] and the MM density (56.41 +/- 6.78) in group B were significantly higher. The UAE [(0.56 +/- 0.72) mg], the GBM thickening [(315.8 +/- 21.4) nm] and the MM density (37.97 +/- 7.37) in group C were significantly lower than those in group B (all were P < 0.01). The renal mRNA expression of FN in group B (0.73 +/- 0.26) was significantly higher than that in group A (0.31 +/- 0.15, P < 0.01), while the expression in group C (0.26 +/- 0.06) was lower than that in group B (P < 0.01).


CONCLUSIONS
NF-kappaB is activated in the diabetic kidneys. The inhibition of NF-kappaB can slow down the development of DN and decrease the mRNA expression of FN in diabetic kidneys. Our data suggest that NF-kappaB may play an important role in the development of DN.
Ding
Helin
H
Department of Endocrinology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, China. helinding@163.net
Li
Feng
F
Xu
Mingtong
M
Deng
Yiqun
Y
Deng
Qingli
Q
Zhu
Zhenyu
Z
Cheng
Hua
H
Fu
Zuzhi
Z
Wang
Youmin
Y
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D005353:Fibronectins / Q000235:genetics; D008297:Male; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology*
D005353:Fibronectins; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid