Kinin B_2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis  

作　　者：Pedro Paulo Gattai Fernando Francisco Pazello Mafra Frederick Wasinski Sandro Soares Almeida Marcos Ant?nio Cenedeze Denise Maria Avancini Costa Malheiros Reury Frank Pereira Bacurau Carlos Castilho Barros Niels Olsen Saraiva Camara Ronaldo Carvalho Araujo 

机构地区：[1]Department of Biophysics, Laboratory of Genetics and Exercise Metabolism, Federal University of Sao Paulo-UNIFESP, Sao Paulo, CEP 04039-032, Brazil [2]Federal University of Sao Paulo-UNIFESP, Sao Paulo, CEP 04039-032, Brazil [3]Nephrology Division, Laboratory of Clinical and Experimental Immunology, Federal University of Sao Paulo–UNIFESP, Sao Paulo, CEP 04039-032, Brazil [4]Renal Division, Department of Clinical Medicine, Laboratory of Renal Pathophysiology (LIM-16), Sao Paulo University-USP, Sao Paulo, CEP 04039-032, Brazil [5]School of Arts, Sciences and Humanities, Sao Paulo University-USP, Sao Paulo, CEP 04039-032, Brazil [6]Nutrition Faculty, Federal University of Pelotas, Rio Grande do Sul, CEP 96010-610, Brazil [7]Department of Immunology, Laboratory of Transplantation in Immunobiology, Sao Paulo University-USP, Sao Paulo, CEP 05508-000, Brazil

出　　处：《World Journal of Nephrology》2014年第3期85-91,共7页世界肾病学杂志（英文版）

基　　金：Supported by The National Council of Scientific and Technological Development-CNPq,No.135020/2011-5

摘　　要：AIM： To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. METHODS： We separated 28 C57Bl/6 male mice into 4 groups： untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution （50% v/v, 7 mL/kg）. After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Addi-tionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and infammatory mediators were measured by real-time polymerase chain reaction. RESULTS： Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice （0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P 〈 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P 〈 0.005）, and between untreated B2 knock-out mice and glycerol-treated knockout mice （0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P 〈 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P 〈 0.01）, but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to in-duce a striking increase in kinin B2 receptor expression （〉 30 times, 31.34 ± 8.9） in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treat-ed with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knock-out mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when com-pared to the wild-type glycerol-treated group. CONCLUSION： We conclude that the kinin B2 receptordoes not have a protective role in renal injury.AIM:To investigate a potential protective role of the kinin B2receptor in a glycerol-induced rhabdomyolysis mouse model.METHODS:We separated 28 C57Bl/6 male mice into4 groups:untreated WT animals,untreated B2knockout mice,glycerol-treated WT and glycerol-treated B2knockout mice.Glycerol-treated animals received one intramuscular injections of glycerol solution(50%v/v,7 m L/kg).After 48 h,urine and blood samples were collected to measure creatinine and urea levels.Additionally,kidney samples were extracted for histological evaluation,and the m RNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction.RESULTS:Serum creatinine and urea levels showed differences between untreated wild-type and glyceroltreated wild-type mice(0.66±0.04 vs 2.61±0.53mg/d L,P<0.01;and 33.51±2.08 vs 330.2±77.7mg/d L,P<0.005),and between untreated B2knockout mice and glycerol-treated knockout mice(0.56±0.03 vs 2.23±0.87 mg/d L,P<0.05;and 42.49±3.2vs 327.2±58.4 mg/d L,P<0.01),but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice.Glycerol was able to induce a striking increase in kinin B2receptor expression(>30 times,31.34±8.9)in kidney.Animals injected with glycerol had a higher degree of tubular injury than untreated animals.Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury,with impairment in renal function.However,B2knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers,when compared to the wild-type glycerol-treated group.CONCLUSION:We conclude that the kinin B2receptordoes not have a protective role in renal injury.

关 键 词：KININS acute kidney injury Animal models RHABDOMYOLYSIS Skeletal muscle 

分 类 号：R446.112[医药卫生—诊断学] R692[医药卫生—临床医学]