Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus (DM) and the main cause of end‐stage renal failure. However, the pathogenesis of DKD is complicated. In this study, we found that miR‐124‐3p plays a key role in regulating renal mitochondrial function and explored its possible mechanism in DKD progression by performing a series of in vitro and in vivo experiments. Decreased expression of miR‐124‐3p was found in db/db mice compared to db/m mice. Moreover, miR‐124‐3p down‐regulated FOXQ1 by targeting FOXQ1 mRNA 3′‐UTR in NRK‐52E cells. Also, an increase in FOXQ1 and down‐regulation of Sirt4 were found in db/db mouse kidney and renal tubular epithelial cells cultured with high glucose and high lipid. Overexpression of FOXQ1 could further down‐regulate the expression of Sirt4 and aggravate the damage of mitochondria. Conversely, the knockdown of the FOXQ1 gene induced Sirt4 expression and partially restored mitochondrial function. To verify the effects of miR‐124‐3p on Sirt4 and mitochondria, we found that miR‐124‐3p mimics could up‐regulate Sirt4 and inhibit ROS production and MitoSOX, thus restoring the number and morphology of mitochondria. These results showed that under high‐glucose and high‐lipid conditions, the down‐regulation of miR‐124‐3p induces FOXQ1 in renal tubular epithelial cells, which in turn suppresses Sirt4 and leads to mitochondrial dysfunction, promoting the development of DKD.
Objective To evaluate the variation characteristics of systolic right intraventricular pressure differences (IVPDs) and right intraventricular pressure gradients (IVPGs) in patients with atrial fibrillation(AF) and normal left ventricular ejection fraction (LVEF) by relative pressure imaging (RPI) based on vector flow mapping(VFM),and to investigate their application value in right ventricular function in patients with normal LVEF AF. Methods Thirty-one patients with normal LVEF AF were selected as normal LVEF AF group,and twenty healthy volunteers were selected as control group.Clinical data and echocardiographic images were collected, and conventional left and right ventricular diameter, area, volume and systolic function parameters were measured.IVPDs and IVPGs in isovolumic contraction(IC), early systole(ES) and late systole(LS) were obtained by the VFM technique.The correlation between the IVPDs and IVPGs in the three systolic time phases and the conventional ultrasound parameters was analyzed between the normal LVEF AF group and the control group. Results The systolic IVPDs and IVPGs in the normal LVEF AF group were significantly lower than those in the control group. Correlation analysis showed that ES-IVPGs and IC-IVPGs in patients with normal LVEF AF were positively correlated (P<0.05), and LS-IVPDs and LS-IVPGs were negatively correlated with ES-IVPDs (P<0.01).Left atrial end-diastolic volume (LAEDV) and left atrial end-systolic volume (LAESV) were negatively correlated with IC-IVPGs (P<0.01). The intraobserver correlation coefficients were 0.939, 0.944, and 0.901 for IC-IVPDs, ES-IVPDs, and LS-IVPDs, respectively; and the interobserver correlation coefficients were 0.854, 0.954, and 0.884, respectively. Conclusions The patients with normal LVEF AF had a systolic right ventricular hemodynamics disorder, resulting in decreased IVPDs and IVPGs in each systolic phase. With a more pronounced decrease in IVPGs during IC which can be used as a potential new index to assess right ventricular hemodynamic changes in patients with normal LVEF AF.
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