ACE2对5/6肾切除小鼠肾损伤的保护作用

目的:研究血管紧张素转换酶抑制剂(ACE2)在肾素血管紧张素系统(RAS)过度激活和进行性肾损害的作用并探讨其可能的作用机制。方法:选取雄性ACE2基因敲除(KO)小鼠及野生型(WT)小鼠,随机分成5/6肾脏切除模型组和假手术组,每2周测量血压,12周后检测肾脏损伤指标血肌酐,并对残余肾组织进行PAS染色观察病理变化;用RT-PCR检测肾组织纤维化指标α-SMA和炎症指标TNF-α的表达。结果:与野生型小鼠比较,ACE2基因敲除型小鼠出现血压明显升高,血肌酐增加。PAS染色分析结果提示ACE2基因敲除型小鼠较野生型出现更严重的系膜区增宽,系膜基质增生。用RT-PCR检测肾组织α-SMA和TNF-α的表达变化,提示ACE2基因敲除模型组小鼠肾脏纤维化和炎症因子的表达较野生型模型组小鼠显著增加。结论:ACE2基因敲除组小鼠较野生型小鼠在5/6肾脏切除术后出现更严重的肾脏损伤,血压增高,肾脏炎症和纤维化改变。

The Protective Role of ACE2 in Ranal Injury in Remnant Kidney

Objective:To observe the protective effects and mechanisms of ACE2 in overactivation of renin angiotensin system and progressive damage.Methods:ACE2 WT and KO mice were randomly divided into 5/6 nephrectomy model group and sham-operated group.Blood pressure was measured every 2 weeks.Serum creatinine was detected after 12 weeks.Pathological changes were observed by PAS staining of residual kidney tissues.The expression of fibrosis indexα-SMA and inflammation index TNF-αwas detected by RT-PCR.Results:Compared with wild-type mice,ACE2 knockout mice had significantly higher blood pressure,increased serum creatinine,analysis of PAS indicated that gene-knockout mice had more severe mesenchymal matrix hyperplasia than wild-type mice.The expression ofα-smooth muscle actin(α-SMA)and tumour necrosis factorα(TNF-α)in kidney tissue was detected by RT-PCR,suggesting that the expression of renal fibrosis and inflammatory factors in ACE2 knockout mice was significantly higher than that in WT mice.Conclusion:ACE2 knockout mice have more severe renal injury,higher blood pressure,and worse inflammation and fibrosis than wild type mice after 5/6 nephrectomy.