Cheng Hong, Tian Xue-fei, Dong Hong-rui, Ding Shuang-shuang, Qiu Chang-bin, Chen Yi-pu
Center of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
Zhonghua Yi Xue Za Zhi. 2004 Feb 2;84(3):248-52.
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.
探讨糖尿病肾病大鼠肾组织中内皮素 -1（ET -1）与血管紧张素 II（AngII）之间的相互关系。
对Wistar大鼠行右肾切除手术。两周后，对单侧肾切除的大鼠静脉注射链脲佐菌素（STZ，35 mg/kg）。将糖尿病大鼠随机分为以下四组：DM + bos组（波生坦100 mg/kg/d灌胃）；DM + ena组（依那普利10 mg/kg/d灌胃）；DM + bos + ena组（波生坦和依那普利均按相同剂量灌胃）；DM + veh组（仅灌胃缓冲液）。此外，将未注射STZ的单侧肾切除大鼠作为对照组。每组6只大鼠。20周后，处死大鼠，分别摘取每只大鼠的左肾。分别采用逆转录 - 聚合酶链反应和免疫组织化学染色半定量检测肾组织中血管紧张素原（Ao）、血管紧张素1型受体（AT1R）、前内皮素 -1和内皮素A受体（ETaR）的mRNA表达，以及AngII、AT1R、ET -1和ETaR的蛋白表达。
在未治疗的糖尿病组（DM + veh组）中，与对照组相比，Ao（AII）、AT1R和ET - AR的表达显著上调（mRNA分别上调1.25、1.94和2.56倍，蛋白分别上调2.52、3.84和3.30倍，P < 0.01或P < 0.05）。在三个治疗组，即DM + bos组、DM + ena组和DM + bos + ena组中，与糖尿病组相比，Ao（AII）、AT1R和ET - AR的上调表达显著减弱（mRNA下降38.2%至54.8%，蛋白下降55.3%至69.7%，P < 0.05或P < 0.01）。这三个治疗组之间的抑制率无显著差异（P > 0.05）。在本研究中，所有组之间前内皮素 -1 mRNA和ET -1蛋白的表达无显著变化（P > 0.05）。
内皮素受体拮抗剂或ACE抑制剂均可显著抑制糖尿病大鼠肾组织中AngII、AT1R和ETaR的表达，这表明ET -1与AngII之间存在密切关系和交叉作用。
