安体舒通和缬沙坦对肾小管上皮细胞凋亡的影响

目的探讨醛固酮受体拮抗剂和血管紧张素П-1型受体拮抗剂（AT1Ra）对大鼠单侧输尿管梗阻（UU0）模型肾间质纤维化的影响及其可能机制。方法Wistar大鼠行左侧输尿管结扎术，分为UU0模型组（n=11），安体舒通治疗组（12=12），缬沙坦治疗组（n=11）和安体舒通＋缬沙坦治疗组（n=10）]，同时设假手术对照组（n=7）。术后第14天处死各组大鼠，进行HE和Massod染色，观察肾脏病理变化；比色法测定肾组织丙二醛（MDA）、超氧化物歧化酶（SOD）含量；原位末端标记法（TUNEL）与DNA电泳观察肾小管上皮细胞凋亡情况；Western blotting检测半胱氨酸天门冬氨酸蛋白酶-3（caspase-3）的蛋白表达。结果UU0组与其它组大鼠比较，肾组织MDA含量明显升高，SOD含量显著下降，肾脏病理改变加重，TUNEL染色及DNA琼脂糖凝胶电泳可见大量的肾小管上皮细胞凋亡，肾组织caspase-3的表达明显增加（P〈0．05）。各用药组与UU0组大鼠比较，肾组织MDA含量明显降低，SOD含量升高，肾小管上皮细胞凋亡和肾间质纤维化显著减轻，caspase-3的表达显著减少（P〈0．05）。结论安体舒通和缬沙坦均可显著改善UU0所致的肾间质纤维化，减轻肾小管上皮细胞的凋亡，部分下调肾组织caspase-3的表达，且联合用药效果更为显著。上述作用可能与该药物抑制氧化应激有关。

The effects of spironolactone and valsartan on apoptosis of renal tubular epithelial cell

Objective To investigate the effects and possible mechanisms of spironolac-tone and valsartan on renal interstitial fibrosis of rat unilateral ureteral obstruction(UUO) model.Methods Fifty-one wistar rats were randomly assigned into five groups: SOR group(sham-operated group,n=7);UUO group(operation group,n=11);UUO +SPI group(spironolactone 50mg/(kg.d) by daily gastric gavage after UUO,n=12);UUO+ARB group(valsartan 10mg/(kg.d) by daily gastric gavage after UUO,n=11) and UUO+SPI+ARB group(combined gastric gavage the same dose of spironolactone and valsartan after UUO,n=10).All the rats were killed at 14 days after surgery.Histological changes were observed by HE and Masson staining.Malondialdehyde(MDA) and superoxide dismutase(SOD) content,renal tubular cell apoptosis,western blotting of cysteinyl aspartate specific proteinase-3(caspase-3) were measured.Results UUO induced a significant increase in MDA content,renal tubular cell apoptosis,western blotting of caspase-3 as well as severe morphology changes and a marked decrease in SOD content.However,three treatment groups ameliorated what had mentioned.Conclusions Spironolactone and valsartan significantly alleviate renal tubulointerstitial fibrosis and renal tubular cell apoptosis in obstructed kidney.Spironolactone and valsartan may markedly suppress the production of oxidative stress and the expression of caspase-3,which may be partly related to the caspase-dependent pathways.