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The body is exposed to various organic anions,so it is the best way to remove the toxic substances in the body quickly and effectively.Cross epithelial active transport mediated by organic anion transporter is the rate limiting process.Renal secretion and re-absorption of a variety of endogenous and exogenous organic anions are occurred in the proximal tubular epithelial cells of the organic anion transporter family.The expression of organic anion transporter-1 (OAT1) in proximal tubular epithelial cells plays an important role in the introduction of organic anion into the renal tubular epithelial cells.This article reviewed the renal expression,the substrate and the polymorphism of the organic anion transport protein OAT1,the renal toxicity of adefovir dipivoxil,the interaction between organic anion transporters and drug,and the influence of the renal toxicity on the renal toxicity of adefovir dipivoxil.
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Objective To investigate the effect of p53-gene expression on renal function in rat with low birth weight ( LBW) .Methods Fifteen pregnant rats were randomly assigned into normal group, LBW group, and L-arginine ( L-Arg)-treated group.For normal group, pregnant rats were fed with 21% protein diet during pregnancy.For LBW and L-Arg treated groups, rats were fed with 10%protein diet.After de-livery, all rats were fed with 21%protein diet.For L-Arg-treated group, rats were given a supplementation with L-Arg (200 mg/kg) drinking water during 21 d lactation, other rats were given running water.At the age of 2m, the ultrastructural change in mesangial cell and podocyte was observed with electron microscope. At the age of 7 d, 21 d, 2 m, and 3 m old, the p53 mRNA expression in renal tissues was observed with re-verse transcription polymerase chain reaction ( RT-PCR) , blood and urine were collected to detect biochem-ical indicators of renal function and 24 h-urine protein.Results ⑴At the age of 3 m,the blood urea nitro-gen ( BUN) and urine cretinine ( UCr) in normal group were significantly lower than those in LBW group ( P <0.01).Compared to normal group, the Ucr of LBW group was significantly lower at the age of 2 m ( P<0.05).At the age of 3 m,the Ucr of L-Arg treated group and LBW group was significantly lower ( P <0.05), the level of 24 h-Urine protein was notably increased in LBW group and L-Arg treated group than that in normal group ( P <0.01, P <0.05) .⑵At the age of 3 m,the expression of p53 mRNA in LBW group was higher obviously than that in normal group.There is a significantly negative correlation between the expression of p53 mRNA and the level of Ucr in LBW group ( r =-0.91, P <0.05).⑶ There were mesangial cell proliferation with matrix increase, filtration membrane podocyte reduction, and partially dis-solved in LBW group, the mesangial cell proliferation of L-Arg treated group was decreased compared to that in LBW group.Conclusions The higher expression of p53 gene in LBW group might be one of reasons for the decreased renal function in LBW rats.
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Objective To investigate the effects of losartan on aortic elasticity and remodeling in spontaneously hypertensive rats (spontaneously hypertensive rats SHR). Methods WKY (Wistar - Kyoto ) rats with normal blood pressure and 16 weeks spontaneously hypertensive rats were randomly divided into WKY control group, SHR control group, high dose losartan group (SHR + HL), low doses losartan group (SHR + LL). Each group has six animals which were given normal diet for 24 weeks. Losartan which was dissolved in 10 ml physiological saline was filling in stomach, other groups were filling with physiological saline. Tail arterial blood pressure, kidney tissues calcium concentration, renal small artery hydroxyproline content was measured and small arteries wall thickness of Glomerularwas detected, and the ratio of thickness and inner diameter (MT/LR) in kidney pathological were observed. Results The calcium concentration of SHR group in kidney tissues was [(18.42±2.34)μmol/g], kidney small artery hydroxyproline content was [(8.26±2.02)mg/g], which were greater than WKY group [(11.83±1.98)μmol/g,(5.16±0.98)mg/g] (t＝3.116,3.258,P＜0.05), but the two treatment groups were less than SHR group (t＝2.946,P＜0.05), the difference was significant. Small arteries wall thickness of Glomerular was [(5.25±1.13)μm], the ratio of thickness and inner diameter (MT/LR) was [(9.57±1.78)%], which were greater than WKY group[(4.03±0.16)μm ,(7.12±1.35)%](t＝2.836,3.425,P＜0.05), but the wall thickness of two treatment groups were [(7.64±1.29)%,(7.85±1.32)%], the two treatment groups were less than SHR group (t＝3.512,3.648,P＜0.05). Conclusions Losartanmay inhibit intracellular calcium overload, reduce fibrosis degree and improve renal arteriole resistance and reverse the renal arteriole reconstruction of SHR rats.
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Objective To investigate the effect of angiotensin Ⅱ (AngⅡ) type 1 receptor block irbesartan on the expression of renal cyclooxygenase-2 ( COX-2 ) in rats with type 2 diabetes mellitus.Methods 18 rats were divided into control group, diabetes mellitus group and treating group.Immunohistochemistry was used to measure the expression of COX-2, matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1).The urinary TXB2,6-Ket-PGF1 αconcentration was determined by radioimmunoassay at the 6th week .Results There was an increasing expression of COX-2,TIMP-1 and decreasing M MP-9 ( COX-2:0.39 ± 0.02 vs 0.24 ± 0.04, TIMP :0.41 ± 0.03 vs 0.24 ± 0.02,MMP-9:0.24 ± 0.02 vs 0.32 ± 0.02, P ＜ 0.05 ) expression in the diabetes mellitus group ( P ＜ 0.05 ).Irbesartan could increase MMP-9 (0.29 ± 0.03 ) and depress TIMP-1 (0.34 ± 0.02) expression through inhibiting the expression of COX-2(0.31 ± 0.03) in renal tissue.Conclusions COX-2 was involved in the pathogenesis of the injury of type 2 diabetic nephropathy.Irbesartan might exert its renoprotective effects through inhibiting COX-2 activity, modulating the expression of MMP-9 and TIMP-1.
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Objective To investigate the change of AQP1 and AQP2 before and after the release of obstruction and explore the relationship between reabsorption dysfunction of renal tubule and the change of AQPs. Methods The model of unilateral ureter obstruction (UUO) was established by surgery. Western blot and immunohistochemistry were used to study the expression of AQPs before and after obstruction. Results In UUO model, both AQPs began to down-regulate one day after obstruction, the expression of both AQPs became lower one day after the release of obstruction. And they started to up-regulate 7 day after the release of obstruction. AQP2 became normal since 14 days after the release of obstruction, and AQP1 became normal since 21 days after the release of obstruction. Conclusion The expression of AQP1 and AQP2 were descended in hydronephrosis. The dysfunction of renal tubule and the osmotic-dependent polyuria after the release of obstruction in UUO were caused by the down - regulation of AQPs.