Abstract:Objective To evaluate the effect of valsartan on apoptosis of podocytes,GRP78 which serve as a symbolic protein of endoplasmic reticulum stress (ERS) and caspase12 in diabetic rats. Methods Male SD rats were randomly divided into normal group and study group.The animal models with diabetes were established in study group by STZ intraperitoneal injection,then the study group were randomly divided into model group and valsartan group.Water was aiministered daily by gavage to normal group and model group.Valsartan was administered daily by gavage to valsartan group for 6 weeks. The levels of protein of nephrin、GRP78,caspase 12.BG,Cr ,BUN and 24-hour urinary protein quantity were checked. Results At the time of 6 weeks,compared with those in normal group,the number of apoptosis cells were much higher in the model kidneys,the expression of GRP78(6.75±0.65),caspase 12 (11.51±0.32)in the model kidneys were much higher than GRP78(1.57±0.39),caspase12(2.66±0.57)in the normal group(P<0.05);however, the expression of nephrin in the model group(2.29±0.15)was lower than in the normal group(5.71±0.53)(P<0.05). While in the valsartan group,reductions were found in the expression of GRP78(3.14±1.00),caspase12 (8.08±2.48)and the number of apoptotic cells(P<0.05),the expression of nephrin (3.35±0.40)was higher(P<0.05). Conclusions Valsartan can depress the effect of endoplasmic reticulum stress and reduce the apotosis of the podocytes in the development of diabetic nephropathy.
Chen M, Felix K, Wang J.Immune regulation through mitochondrion-dependent dendritic cell death induced by T regulatory cells [J].J Immunol,2011,187(11):5684-5692.
[1]
Toycda M, Suzuki D. Expression of human nephrin mRNA in diabetic nephropathy[J]. Nephrol Dial Transplant,2004,19(3):380-385.
[4]
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response[J].Nat Rev Mol Cell Biol,2007, 8(7):519-529.
[2]
Butt A, Riaz S.Study of protein profiling of human urine in diabetic hypertensive nephropathy versus normal healthy controls[J].Diabetes Technol Ther, 2010,12(5):379-386.
[5]
Kriz W. Progressive renal failure-inability of podocytes to replicate and the consequences for development of glomerulosckerosis[J].Nephrol Dial Transplant,1996,11(9):1738-1742.
[3]
Chen M, Felix K, Wang J.Immune regulation through mitochondrion-dependent dendritic cell death induced by T regulatory cells [J].J Immunol,2011,187(11):5684-5692.
[6]
Liu G, Sun Y, Li Z,et al. Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease [J].Biochem Biophys Res Commun,2008,13,370(4):651-656.
[4]
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response[J].Nat Rev Mol Cell Biol,2007, 8(7):519-529.
[5]
Kriz W. Progressive renal failure-inability of podocytes to replicate and the consequences for development of glomerulosckerosis[J].Nephrol Dial Transplant,1996,11(9):1738-1742.
[7]
Schroder M, Kaufman R J.The mammalian unfolded protein response[J]. Annu Rev Biochem,2005,74:739-789.
[6]
Liu G, Sun Y, Li Z,et al. Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease [J].Biochem Biophys Res Commun,2008,13,370(4):651-656.
[8]
Ni M, Lee A S.Echaperones in mammalian development and human diseases[J].FEBS Lett,2007,581(19):3641-3651.
[7]
Schroder M, Kaufman R J.The mammalian unfolded protein response[J]. Annu Rev Biochem,2005,74:739-789.
[9]
Ohse T, Inagi R, Tanaka T,et al. Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells[J].Kidney Int,2006,70(8):1447-1455.
[10]
Davis B J, Cao Z, Gaparo M,et al.Disparate effects of angiotensin Ⅱ antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension:potential role of nephrin[J]. Hypertens,2003,21(1):209-216.
[8]
Ni M, Lee A S.Echaperones in mammalian development and human diseases[J].FEBS Lett,2007,581(19):3641-3651.
[11]
Davis B J, Forbes J M, Thomas M C, et al.Superior renoprotective effects of combination therapy with ACE and AGE inhibition in the diabetic spontaneously hypertensive rat[J].Diabetologia,2004,47(1):89-97.
[9]
Ohse T, Inagi R, Tanaka T,et al. Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells[J].Kidney Int,2006,70(8):1447-1455.
Davis B J, Cao Z, Gaparo M,et al.Disparate effects of angiotensin Ⅱ antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension:potential role of nephrin[J]. Hypertens,2003,21(1):209-216.
[11]
Davis B J, Forbes J M, Thomas M C, et al.Superior renoprotective effects of combination therapy with ACE and AGE inhibition in the diabetic spontaneously hypertensive rat[J].Diabetologia,2004,47(1):89-97.