[Effects of lovastatin on renal function and expression of phosphorylating-p38 mitogen-activated protein kinase in experimental diabetic nephropathy in rats].
OBJECTIVE
To investigate the effects of lovastatin on renal function, activity and expression of the p38 mitogen-activated protein kinase (MAPK) and cAMP responsive element-binding protein (CREB) in experimental diabetic nephropathy in rats.


METHODS
Eighteen uninephrectomized male Wistar rats were randomly divided into three groups: control (n=6), diabetic (n=6) and lovastatin treatment group (n=6). Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg). Lovastatin (20 mg/kg) was administered daily by gavage from the next day of the induction diabetes for 4 weeks. Four weeks later, animals were sacrificed and samples were collected to determine various parameters, including protein and creatinine in urine (Upro and UCr), and glucose (Glu), creatinine (SCr), blood urea nitrogen (BUN) in serum. Immunohistochemistry and computer image-pattern analysis system were used to analyze activation of P-p38 MAPK and P-CREB, the expression of transferase growth factor-beta(1) (TGF-beta(1)), fibronectin (FN), laminin (LN) in renal glomeruli were also measured.


RESULTS
Expression of P-p38 MAPK and P-CREB in diabetic glomeruli in diabetic rats were higher than the controls, the same as the expression of TNF-beta(1), FN, LN(all P<0.01). After lovastatin treatment, expression of P-p38 MAPK, P-CREB and TGF-beta(1), FN, LN were markedly decreased compared with diabetic group(all P<0.01).


CONCLUSIONS
Inhibition of glomerular p38 MAPK signal transduction pathway may be responsible for the decrement of extracellular matrix accumulation and renal protective effects of lovastatin in uninephrectomized rats.
Wang
Li-hui
LH
Department of Pathology, Hebei Medical University, Shijiazhuang 050017, Hebei, China.
Duan
Hui-jun
HJ
Shi
Yong-hong
YH
Liu
Qing-juan
QJ
He
Ning
N
Liu
Shu-xia
SX
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D008148:Lovastatin; D048051:p38 Mitogen-Activated Protein Kinases