ACE2激活剂DIZE对运动性肾损伤小鼠Ang Ⅱ/Ang1-7的影响

EFFECT OF ACE2 ACTIVATOR DIZE ON ANG Ⅱ/ANG1-7 IN RENAL INJURY OF EXHAUSTIVE TRAINING MICE

目的观察给予ACE2激活剂三氮脒(diminazene aceturate,DIZE)后,力竭运动致小鼠肾损伤情况及AngⅡ/Ang1-7水平的变化。方法 24只C57野生小鼠随机分为四组:正常对照组(C组)、DIZE对照组(D组)、力竭训练组(ET组)、DIZE+力竭训练组(DT组)。实验通过力竭跑台运动建立小鼠运动性肾损伤模型,给予DIZE(10mg/kg,皮下注射)进行干预,采用比色法检测血肌酐、血尿素氮、肾组织MDA及SOD,ELISA法检测AngⅡ、Ang1-7水平;免疫组化法观察肾组织ACE2蛋白表达;HE染色观察肾脏病理改变。结果与C组比23较,ET组小鼠血浆肌酐、尿素氮水平升高;肾组织MDA明显升高、SOD明显降低;血浆及肾组织AngⅡ水平明显升高,Ang1-7降低;肾组织ACE2蛋白表达降低(均P<0.05);肾组织HE染色显示部分肾小球缩小,肾小囊扩张,肾小管扩张明显,小管上皮细胞水肿、崩解等肾损伤病理。DT组与ET组小鼠比较,肾功能相关指标血浆肌酐、尿素氮明显下降;肾组织MDA明显降低、SOD明显提高(均P<0.05);血浆及肾组织AngⅡ降低(均P<0.05),血浆Ang1-7水平显著升高,肾组织Ang1-7水平有升高趋势但差异无统计学意义(P>0.05);肾组织病理损伤减轻。结论过度跑台运动可致小鼠肾损伤;DIZE可能通过激活ACE2,降低AngⅡ、提高Ang1-7水平,减轻肾组织氧化应激,在过度训练小鼠肾损伤过程中发挥保护作用。

Objective To observe the effect of Diminazene aceturate （DIZE） on renal injury in exhaustive training mice. Methods Twenty- four C57 mice were randomly divided into four groups： control group （CI, DIZE control group （DI , exhaustive training group （ET）, DIZE 4- exhaustive training group （DT/. The experimental model was set up by exhaustive training. DIZE （10mg/kg per day, s. c. ） was injected in. The levels of serum creatinine （Scr） and blood urianitrogen （BUN）, malondialdeyde （MDA） and superoxide dismutase （SOD） in kidney were detected by chemical colorimetric method. Ang Ⅱ and Angl -7 contents in blood and kidney were detected by ELISA. The expression of ACE2 in kidney tissues was tested by immuno - histochemistry method. HE staining of histopathological changes of renal was detected with optical microscope. Results Compared with C group, in ET group the levels of Scr, BUN, MDA in renal, AngⅡ in kidney and blood were significantly increased, the level of SOD, Angl- 7 and the expression of ACE2 in kidney tissues was also increased, damaging changes in renal structure were observed after exhaustive training. Scr, BUN, MDA and Ang Ⅱ were decreased gradually in DT group compared with ET group, but the level of SOD, Angl - 7 and the expression of ACE2 in kidney was increased significantly. Patholo- gical damage improved obviously in DT group. Conclusions Exhaustive training can cause renal injury in mice. DIZE may have protective effect on renal injury in exhaustive training mice by increaseing the expression of ACE2, regulating AngⅡ/ Angl - 7, and by decreasing the generation of oxygen free radicals.