外源性apelin对大鼠低氧性肾早期纤维化作用的初步观察

Effect of Apelin on Early Renal Interstitial Fibrosis Induced by Hypoxia in Rats

目的探讨外源性小分子活性肽apelin对大鼠低氧性肾间质纤维化的防治作用及其机制。方法30只雄性SD大鼠随机均分为3组：正常对照组、低氧组和低氧＋apelin组。Apelin组通过皮下埋植微量渗透泵持续给予[pGlu]apelin-13（10nmol／kg／d）。低氧4周后，测定血清肌酐（Scr）、尿素氮（BUN）含量以及肾组织羟脯氨酸（Hyp）、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，VG染色观察肾间质纤维化情况。结果①各组间血清BUN及Scr无显著性差别；②肾组织Hyp含量：低氧组较正常对照组高35．4％（P〈0．01），而apelin组较低氧组低24．6％（P〈0．05）；③MDA含量：低氧组较正常对照组高38．9％（P〈0．01），而apelin组较低氧组低55．7％（P〈0．01）；SOD活性：低氧组较正常对照组低55．1％（P〈0．01），但apelin组较低氧组高20．7％（P〈0．01）；④VG染色显示低氧组肾血管胶原纤维增生明显，而apelin组明显改善。结论Apelin对低氧大鼠肾间质纤维化具有防治作用，这种作用可能与调节氧化-抗氧化失衡有关。

Objective To study the role of apelin in the prevention of renal interstitial fibrosis induced by hypoxia in rats. Methods The animal model of hypoxic renal interstitial fibrosis was established by exposing the rats to isobaric hypoxic chamber for 4 weeks （8h/d, 6d/week）. Thirty male Sprague-Dawley rats were randomly divided into control group, hypoxic group and hypoxia with apelin （10nmol/kg/d） group （HA）. [pGlu]apelin-13 was administered into the rats of apelin groups by mini-osmotic pump subcutaneously. Serum creatinine （Scr） and urea nitrogen （BUN） were measured. The renal homogenates were assayed for the activity of superoxide dismutase （SOD） and the contents of malondialdehyde （MDA） and hydroxyproline. Meanwhile, the renal specimens were examined by VG staining to examine renal interstitial fibrosis. Results （1） There was no significant difference of Scr and BUN among three groups. （2） The content of hydroxyproline in hypoxic group was 35.4%（P〈0.01） higher than that of control group, while apelin group was 24.6%（P〈0.05） lower than hypoxic group. （3） The activity of SOD in hypoxic group was lower than that in control group by 55.1% while the content of MDA was higher by 38.9% （all P〈0.01）. Apelin treatment increased the activity of SOD by 20.7% （P〈0.01） while decreased the content of MDA by 55.7 （all P〈0.01）. （4） VG staining revealed that renal vascular fibrosis was found in hypoxia groups, which was significantly alleviated by apelin treatment. Conclusions Apelin could play an important role in treatment of hypoxic renal interstitial fibrosis of rats, and the mechanisms of protection were associated with inhibition of oxidative stress.