Early application of Mdivi-1 protects kidney in rats against uncontrolled hemorrhagic shock

Abstract

Objective To determine the protective effect of early application of Mdivi-1, an inhibitor of mitochondrial division, on the kidneys of rats with uncontrolled hemorrhagic shock after maintaining hypotensive resuscitation. Methods A total of 128 SD rats were randomly divided into 4 groups: sham operation group (Sham group), uncontrolled hemorrhagic shock group (Shock group), conventional fluid resuscitation group (Ct group), and conventional fluid resuscitation combined with Mdivi-1 treatment group (Mdivi-1 group). The changes of survival rate, survival time, renal function, renal blood flow and mitochondrial function in above groups were observed and compared. Results ① The survival time of the rats was longer in the Ct group than the Shock group. The Mdivi-1 group had significantly longer survival time (51.7 h) and 72-hour improvement (31.25%) when compared with the Ct group (14.4 h, 0%; P < 0.05). ② Though the renal blood flow of rats was improved in the Ct group than the Shock group (P < 0.05), while the improving effect was more obvious in the Mdivi-1 group as compared to the Ct group (128.43±25.55 vs 244.76±57.79 U/min, P < 0.01). ③Mdivi-1 group showed significantly lower levels of serum creatinine (Crea) and urea nitrogen (Urea) than the Shock group (P < 0.01) and the Ct group (P < 0.05); ④Mdivi-1 significantly improved the renal mitochondrial respiratory control rate (RCR), which was statistically higher than those of the Shock group and Ct group (P < 0.05); ⑤Compared with the Shock group and the Ct group, the Mdivi-1 group had significantly decreased contents of renal malondialdehyde (MDA) and reactive oxygen species (ROS) (P < 0.01), indicating its great alleviation to the injury of uncontrolled hemorrhagic shock. Conclusion Prior to definitive hemostatic therapy for uncontrolled hemorrhagic shock, the administration of mdivi-1 in combination with routine fluid resuscitation can effectively increase the survival rate, improve renal perfusion and renal function as well as renal mitochondrial function, and consequently reduce oxidative stress injury in rats.

Keywords

• uncontrolled hemorrhagic shock
• inhibitors of mitochondrial division
• maintanance of hypotensive resuscitation