Icariin improves acute kidney injury and proteinuria in a rat model of pregnancy-induced hypertension

Icariin has previously been demonstrated to attenuate hyperglycemia-induced renal injury, however the renoprotective effects of icariin in a rat model of pregnancy-induced hypertension (PIH) remain to be elucidated. The present study aimed to investigate the effect of icariin on PIH-induced acute kidney injury (AKI) and proteinuria. Following 18 days of icariin treatment between day 1 and day 18 of gestation, which was combined with NG-nitro-L-arginine methyl ester (L-NAME) treatment between day 12 and day 18 of gestation to induce PIH, the 24 h urine protein level, blood urea nitrogen and serum creatinine were measured by using the Coomassie Brilliant Blue method, a commercial enzymatic kit and the picric acid method, respectively. Renal tissues were collected at day 18 of gestation for hematoxylin and eosin staining and immunohistochemistry. The mRNA expression of AGT and protein expression of angiotensin II (Ang II) in the kidneys of control and PIH rats was investigated by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively, to determine the effect of icariin on components of the renin-angiotensin system. The results demonstrated that L-NAME treatment in pregnant rats resulted in significant increases in systolic blood pressure (SBP) and diastolic blood pressure, in addition to the induction of severe proteinuria. The significant increase in SBP and proteinuria in PIH rats was prevented by icariin. L-NAME-induced AKI resulted in profound renal histological alterations, including mesangial expansion and glomerular lesions. L-NAME administration exerted a marked decrease in the mRNA and protein expression levels of nephrin in the kidneys from PIH rats compared with control group. Furthermore, upregulation of circulating and renal Ang II levels in PIH rats was observed. However, icariin treatment significantly reversed the L-NAME-induced downregulation of nephrin and upregulation of circulating and renal Ang II levels in PIH rats. These results demonstrated that icariin administration improved urinary protein excretion levels and renal tissue damage in PIH rats, and the underlying mechanism was mediated in part, via upregulation of nephrin expression and downregulation of Ang II.