Expression of tissue inhibitor of metalloproteinases 1 in chronic renal failure rats with arterial calcification
10.3760/cma.j.issn.1001-7097.2009.05.013
- VernacularTitle:金属蛋白酶1组织抑制剂在慢性肾衰竭大鼠钙化动脉中的表达
- Author:
Jie FENG
;
Hongli LIN
;
Taihua WU
;
Yanling SUN
;
Lu WANG
- Publication Type:Journal Article
- Keywords:
Tissue inhibitor of metalloproteinases- 1;
Kidney failure,Chronic;
Corebinding factors;
Vascular calcification
- From:
Chinese Journal of Nephrology
2009;25(5):369-374
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine whether tissue inhibitor of metalloproteinases-1 (TIMP-1) is involved in arterial calcification of chronic renal failure (CRF) rats. Methods CRF model was induced in male Wistar rats by garage daily with 2% adenine 250 mg/kg. The calcification of aorta, femoral artery, renal artery and coronary artery was evaluated histomorphometrically by van Kossa-stained sections at 2-, 4-, 6- and 8-week respectively. RT-PCR and Western blot were used to observe the expressive levels of TIMP-1 mRNA and protein. Expressions of TIMP-1, osteopentin (OPN) and core binding factor α1 (Cbfα-1) protein were analyzed by immunhistochemistry. Results Serum urea nitrogen, creatinine, inorganic phosphate, calcium-phosphorus product and intact parathyroid hormone (iPTH) increased significantly in the model animals compared with control group after 2 weeks (P<0.01). Medial calcification was found in above four arteries of model groups after 6 weeks. RT-PCR and Western blot showed that TIMP-1 expression of model group was significantly higher than that of control group (P< 0.05), and obviously elevated in a time-dependent manner. The expression of TIMP-1 and OPN in calcified aortic smooth muscle cells increased obviously (P<0.05), and positive immunostaining of Cbfα-1 was found. The expression of TIMP-1 was positively correlated with OPN and Cbfα-1 (r=0.317, P=0.000; r=0.485, P=0.000). Conclusions The pathology of arterial calcification in CRF rats induced by adenine is similar to CRF patients, which may serve as a useful model of CRF with arterial calcification. The up-regulation of TIMP-1 seems to participate in the formation and development of vascular calcification in CRF.
