Mechanism of magnesium sulfate suppressing vascular calcification in rats with chronic renal failure through TLR4/NF-κB pathway
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Abstract
Objective To explore the effect of magnesium sulfate on vascular calcification(VC) in rats with chronic renal failure(CRF)through the pathway of Toll-like receptor 4(TLR4) /nuclear transcription factor-κB(NF-κB). Methods A total of 50 Sprague-Dawley(SD)rats were randomized into five groups of control,model,magnesium sulfate-L(25% magnesium sulfate,2 mL),magnesium sulfate-H(25% magnesium sulfate,4 mL)and magnesium sulfate-H+PDTC(25% magnesium sulfate,4 mL+NF-κB inhibitor PDTC,100 mg/kg) (n=10 each). Except for control group,model rats received adenine sulfate suspension by gavage for 3 weeks. From 4 to 12 weeks,magnesium sulfate-L, magnesium sulfate-H and magnesium sulfate-H+PDTC(pyrrolidine dithiocarbamate)had a gavage of corresponding doses of drugs. Model group received an equal volume of normal saline by gavage(once daily)and a high-phosphorus feed throughout;control group received 1.5% methylcellulose by gavage for 1-3 weeks,the same amount of normal saline by gavage for 4-12 weeks and basal feed during trial period;serum biochemical parameters were detected by an automatic biochemical analyzer;the pathology of kidney tissue was observed with hematoxylin-eosin(HE)stain;calcification of abdominal aorta was observed with von Kossa stain;calcium content in abdominal aortic vessel wall was detected by ocresolphthalein complex ketone colorimetry;the expressions of core binding factor α1(Cbfα1),bone morphogenic protein 2(BMP2)and TLR4/NF-κB pathway proteins in abdominal aorta were assayed by Western blot. Results As compared with control group,the levels of blood urea nitrogen(BUN),serum creatinine(Scr),blood phosphorus,calcium,degree of renal tissue pathological injury,abdominal aortic calcification and the expressions of Cbfα1,BMP2,TLR4,p-NF-κB p56/NF-κB p56 spiked markedly in model group while serum level of magnesium declined sharply(P<0.05);compared with model group,the levels of BUN,Scr,blood phosphorus,calcium,renal histopathology,abdominal aortic calcification and expressions of Cbfα1,BMP2,TLR4 and p-NF-κB p56/NF-κB p56 declined markedly in magnesium sulfate-L,magnesium sulfate-H and magnesium sulfate-H+PDTC groups while the level of magnesium rose significantly (P<0.05);compared with magnesium sulfate-L group,the levels of BUN,Scr,blood phosphorus,calcium,degree of renal tissue pathological injury,abdominal aortic calcification and expressions of Cbfα1,BMP2,TLR4,p-NF-κB p56/NF-κB p56 declined markedly in magnesium sulfate-H and magnesium sulfate-H+PDTC groups while the level of magnesium increased obviously(P<0.05);compared with magnesium sulfate-H group,the levels of BUN,Scr,blood phosphorus,calcium,renal histopathology,abdominal aortic calcification and the expressions of Cbfα1,BMP2, TLR4,p-NF-κB p56/NF-κB p56 dropped obviously in magnesium sulfate-H+PDTC group while the level of magnesium increased significantly(P<0.05). Conclusion Magnesium sulfate may improve the status of VC of CRF through suppressing the TLR4/NF-κB pathway in rats.
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