Publications (2)0 Total impact
Article: [The preliminary studies on the cross action between endothelin-1 and angiotensin II in kidney tissue of rats with diabetic nephropathy].[show abstract] [hide abstract]
ABSTRACT: To investigate the interrelation between endothelin-1 (ET-1) and angiotensin II (AngII) in kidney tissue of rats with diabetic nephropathy. Wistar rats were performed a removal operation of right kidney. Two weeks later the uninephrectomized rats were given intravenous injection of streptozotocin (STZ, 35 mg/kg). The diabetic rats were randomly divided into the following four groups: DM + bos group (bosentan 100 mg/kg/d by gavage); DM + ena group (enalapril 10 mg/kg/d by gavage); DM + bos + ena group (the same doses of both bosentan and enalapril by gavage); DM + veh group (only buffer by gavage). Besides, uninephrectomized rats without STZ injection were assigned as control group. Each group consisted of 6 rats. Twenty weeks later, they were sacrificed and left kidney of each rat was harvested respectively. The mRNA expression of angiotensinogen (Ao), angiotensin type 1 receptor (AT1R), preproendothelin-1 and endothelin A receptor (ETaR), and the protein expression of AngII, AT1R, ET-1 and ETaR in kidney tissue were semi-quantitatively detected with reverse transcription- polymerase chain reaction and immunohistochemical staining respectively. In the diabetic group without treatment (DM + veh group), the expression of Ao (AII), AT1R and ET-AR was significantly up-regulated (1.25, 1.94 and 2.56-folds in mRNA respectively, 2.52, 3.84 and 3.30-folds in protein respectively, P < 0.01 or P < 0.05) compared with control group. In three treatment groups, i.e. DM + bos group, DM + ena group and DM + bos + ena group, the up-regulated expression of Ao (AII), AT1R and ET-AR was significantly attenuated (-38.2% to -54.8% in mRNA and -55.3% to -69.7% in protein, P < 0.05 or P < 0.01) compared with DM group. The inhibitory rates among these three treatment groups had no significant difference (P > 0.05). In this study, the expression of preproendothelin-1 mRNA and ET-1 protein was not significantly changed among all groups (P > 0.05). Either endothelin receptor antagonist or ACE inhibitor can significantly inhibit the expression of AngII, AT1R and ETaR in kidney tissue of diabetic rats, which suggest that there are close relationship and cross action between ET-1 and AngII.Zhonghua yi xue za zhi 02/2004; 84(3):248-52.
Article: [Renoprotective effects of nonselective endothelin receptor antagonist bosentan on rats with interstitial fibrosis following unilateral ureteral obstruction].[show abstract] [hide abstract]
ABSTRACT: To investigate the effects of nonselective endothelin receptor antagonist bosentan on the progression of renal interstitial fibrosis following unilateral ureteral obstruction (UUO). Eighteen female SD rats were randomly divided into 3 groups: intervention group (administered with bosentan for 7 days after left ureter ligation), animal model group (administered with solution of Arabic gum for 7 days left ureter ligation) and sham operation group (administered with Arabic gum for 7 days after sham operation). Seven days after the operation the rats were killed and their left kidneys were harvested. The mRNA expressions of preproendothelin-1 (prepro ET-1), type I collagen (ColI), transforming growth factor beta1 (TGF-beta1), tissue inhibitors of metalloproteinase-1 (TIMP-1) and type 1 plasminogen activator inhibitor (PAI-1) were detected semiquantitatively with reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of endothelin-1 (ET-1), ColI, TGF-beta1, TIMP-1 and PAI-1were determined semiquantitatively by immunohistochemical staining assay. The mRNA expressions of prepro ET-1, ColI, TGF-beta1, TIMP-1 and PAI-1 were significantly upregulated in obstructed renal tissue compared to those in sham operation group (all P < 0.05). The positive staining areas of ET-1, ColI, TGF-beta1, TIMP-1 and PAI-1 in tubulointerstitium were markedly enhanced in the animal model group in comparison with those in the sham operation group (all P < 0.05). The mRNA expressions of ColI, TGF-beta1 and TIMP-1 in renal tissue subjected to ureter ligation were significantly lower in the bosentan group then in the animal model group (all P < 0.05). The positive staining areas of ColI, TGF-beta1 and TIMP-1 in the tubulointerstitium were significantly smaller in bosentan group than in the animal model group (all P < 0.05). However, there was no significant difference in the mRNA expression of PAI-1 and in the positive staining area between the animal model group and bosentan group (both P > 0.05). ET-1 may be involved in the progression of renal interstitial fibrosis following unilateral ureter ligation and blockage of its receptors with bosentan attenuates the fibroticlesion to a certain extent by possibly inhibiting TGF-beta1 and TIMP-1.Zhonghua yi xue za zhi 04/2003; 83(6):510-4.