早期应用Mdivi-1对非控制失血性休克大鼠肾脏的保护作用

房贺; 佘汉; 李涛; 刘良明; 朱娱; 吴跃; 胡弋

doi:10.16016/j.1000-5404.202010097

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早期应用Mdivi-1对非控制失血性休克大鼠肾脏的保护作用

基础医学 | 更新时间：2026-01-09

- 早期应用Mdivi-1对非控制失血性休克大鼠肾脏的保护作用
- Early application of Mdivi-1 protects kidney in rats against uncontrolled hemorrhagic shock
- 第三军医大学学报 2021年43卷第6期页码：467-472
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202010097
  中图分类号：
- 收稿：2020-10-16，
  
  纸质出版：2021-03-30
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房贺, 佘汉, 李涛, 等. 早期应用Mdivi-1对非控制失血性休克大鼠肾脏的保护作用[J]. 第三军医大学学报, 2021,43(6):467-472.

He FANG, Han SHE, Tao LI, et al. Early application of Mdivi-1 protects kidney in rats against uncontrolled hemorrhagic shock[J]. Journal of Third Military Medical University, 2021, 43(6): 467-472.
房贺, 佘汉, 李涛, 等. 早期应用Mdivi-1对非控制失血性休克大鼠肾脏的保护作用[J]. 第三军医大学学报, 2021,43(6):467-472. DOI： 10.16016/j.1000-5404.202010097.

He FANG, Han SHE, Tao LI, et al. Early application of Mdivi-1 protects kidney in rats against uncontrolled hemorrhagic shock[J]. Journal of Third Military Medical University, 2021, 43(6): 467-472. DOI： 10.16016/j.1000-5404.202010097.

摘要

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%;

0.05). ② Though the renal blood flow of rats was improved in the Ct group than the Shock group (

0.05)

while the improving effect was more obvious in the Mdivi-1 group as compared to the Ct group (128.43±25.55

244.76±57.79 U/min

0.01). ③Mdivi-1 group showed significantly lower levels of serum creatinine (Crea) and urea nitrogen (Urea) than the Shock group (

0.01) and the Ct group (

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 (

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) (

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.

关键词

Keywords

references

DU Z M JIA H P LIU J Effects of three hydrogen-rich liquids on hemorrhagic shock in rats J Surg Res 2015 193 1 377 382 10.1016/j.jss.2014.06.051 DU Z M, JIA H P, LIU J, et al . Effects of three hydrogen-rich liquids on hemorrhagic shock in rats[J ] . J Surg Res, 2015, 193(1): 377-382. DOI: 10.1016/j.jss.2014.06.051.

XU J LAN D LI T Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway Cardiovasc Res 2012 96 2 308 319 10.1093/cvr/cvs254 XU J, LAN D, LI T, et al . Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway[J ] . Cardiovasc Res, 2012, 96(2): 308-319. DOI: 10.1093/cvr/cvs254.

ZHANG N WANG S LI Y A selective inhibitor of Drp1, mdivi-1, acts against cerebral ischemia/reperfusion injury via an anti-apoptotic pathway in rats Neurosci Lett 2013 535 104 109 10.1016/j.neulet.2012.12.049 ZHANG N, WANG S, LI Y, et al . A selective inhibitor of Drp1, mdivi-1, acts against cerebral ischemia/reperfusion injury via an anti-apoptotic pathway in rats[J ] . Neurosci Lett, 2013, 535: 104-109. DOI: 10.1016/j.neulet.2012.12.049.

LI T LIN X ZHU Y Short-term, mild hypothermia can increase the beneficial effect of permissive hypotension on uncontrolled hemorrhagic shock in rats Anesthesiology 2012 116 6 1288 1298 10.1097/aln.0b013e318256f09d LI T, LIN X, ZHU Y, et al . Short-term, mild hypothermia can increase the beneficial effect of permissive hypotension on uncontrolled hemorrhagic shock in rats[J ] . Anesthesiology, 2012, 116(6): 1288-1298. DOI: 10.1097/aln.0b013e318 256f09d.

ZHAO B FEI J CHEN Y Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1 BMC Complement Altern Med 2014 14 442 10.1186/1472-6882-14-442 ZHAO B, FEI J, CHEN Y, et al . Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1[J ] . BMC Complement Altern Med, 2014, 14: 442. DOI: 10.1186/1472-6882-14-442.

ERIKSSON M BRATTSTRÖM O MÅRTENSSON J Acute kidney injury following severe trauma: Risk factors and long-term outcome J Trauma Acute Care Surg 2015 79 3 407 412 10.1097/TA.0000000000000727 ERIKSSON M, BRATTSTRÖM O, MÅRTENSSON J, et al . Acute kidney injury following severe trauma: Risk factors and long-term outcome[J ] . J Trauma Acute Care Surg, 2015, 79(3): 407-412. DOI: 10.1097/TA.0000000000000727.

SIMS C A YUXIA G SINGH K Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function PLoS ONE 2017 12 10 e0186339 10.1371/journal.pone.0186339 SIMS C A, YUXIA G, SINGH K, et al . Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function[J ] . PLoS ONE, 2017, 12(10): e0186339. DOI: 10.1371/journal.pone.0186339.

BERNARD S A GRAY T W BUIST M D Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia N Engl J Med 2002 346 8 557 563 10.1056/nejmoa003289 BERNARD S A, GRAY T W, BUIST M D, et al . Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia[J ] . N Engl J Med, 2002, 346(8): 557-563. DOI: 10.1056/nejmoa003289.

AYANGA B A BADAL S S WANG Y Dynamin-related protein 1 deficiency improves mitochondrial fitness and protects against progression of diabetic nephropathy J Am Soc Nephrol 2016 27 9 2733 2747 10.1681/asn.2015101096 AYANGA B A, BADAL S S, WANG Y, et al . Dynamin-related protein 1 deficiency improves mitochondrial fitness and protects against progression of diabetic nephropathy[J ] . J Am Soc Nephrol, 2016, 27(9): 2733-2747. DOI: 10.1681/asn.2015101096.

SHARP W W BEISER D G FANG Y H Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model Crit Care Med 2015 43 2 e38 e47 10.1097/ccm.0000000000000817 SHARP W W, BEISER D G, FANG Y H, et al . Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model[J ] . Crit Care Med, 2015, 43(2): e38-e47. DOI: 10.1097/ccm.0000000000000817.

WU Q GAO C WANG H Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation Int J Biochem Cell Biol 2018 94 44 55 10.1016/j.biocel.2017.11.007 WU Q, GAO C, WANG H, et al . Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation[J ] . Int J Biochem Cell Biol, 2018, 94: 44-55. DOI: 10.1016/j.biocel.2017.11.007.

佘汉房贺李涛右美托咪定对脓毒症大鼠血管内皮屏障功能的保护作用第三军医大学学报 2020 42 4 334 341 10.16016/j.1000-5404.201909226 佘汉, 房贺, 李涛, 等. 右美托咪定对脓毒症大鼠血管内皮屏障功能的保护作用[J]. 第三军医大学学报, 2020, 42(4): 334-341. DOI: 10.16016/j.1000-5404.201909226.

SHE H FANG H LI T Protective effect of dexmedetomidine on endothelial barrier function in rats with sepsis J Third Mil Med Univ 2020 42 4 334 341 10.16016/j.1000-5404.201909226 SHE H, FANG H, LI T, et al . Protective effect of dexmedetomidine on endothelial barrier function in rats with sepsis[J ] . J Third Mil Med Univ, 2020, 42(4): 334-341. DOI: 10.16016/j.1000-5404.201909226.

MANEECHOTE C PALEE S KERDPHOO S Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury Clin Sci (Lond) 2018 132 15 1669 1683 10.1042/cs20180510 MANEECHOTE C, PALEE S, KERDPHOO S, et al . Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury[J ] . Clin Sci (Lond), 2018, 132(15): 1669-1683. DOI: 10.1042/cs20180510.

NASH K HAFEEZ A HOU S S Hospital-acquired renal insufficiency Am J Kidney Dis 2002 39 5 930 936 10.1053/ajkd.2002.32766 NASH K, HAFEEZ A, HOU S S.Hospital-acquired renal insufficiency[J]. Am J Kidney Dis, 2002, 39(5): 930-936. DOI: 10.1053/ajkd.2002.32766.

HULTSTRÖM M Neurohormonal interactions on the renal oxygen delivery and consumption in haemorrhagic shock-induced acute kidney injury Acta Physiol (Oxf) 2013 209 1 11 25 10.1111/apha.12147 HULTSTRÖM M. Neurohormonal interactions on the renal oxygen delivery and consumption in haemorrhagic shock-induced acute kidney injury[J]. Acta Physiol (Oxf), 2013, 209(1): 11-25. DOI: 10.1111/apha.12147.

MOREIRA M A IRIGOYEN M C SAAD K R N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock J Surg Res 2016 203 1 113 120 10.1016/j.jss.2016.02.020 MOREIRA M A, IRIGOYEN M C, SAAD K R, et al . N-acetylcys teine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock[J ] . J Surg Res, 2016, 203(1): 113-120. DOI: 10.1016/j.jss.2016.02.020.

CASSIDY-STONE A CHIPUK J E INGERMAN E Chemical inhibition of the mitochondrial division dynamin reveals its role in bax/bak-dependent mitochondrial outer membrane permeabilization Dev Cell 2008 14 2 193 204 10.1016/j.devcel.2007.11.019 CASSIDY-STONE A, CHIPUK J E, INGERMAN E, et al . Chemical inhibition of the mitochondrial division dynamin reveals its role in bax/bak-dependent mitochondrial outer membrane permeabilization[J ] . Dev Cell, 2008, 14(2): 193-204. DOI: 10.1016/j.devcel.2007.11.019.

BASSO E FANTE L FOWLKES J Properties of the permeability transition pore in mitochondria devoid of cyclophilin D J Biol Chem 2005 280 19 18558 18561 10.1074/jbc.c500089200 BASSO E, FANTE L, FOWLKES J, et al . Proper ties of the permeability transition pore in mitochondria devoid of cyclophilin D[J ] . J Biol Chem, 2005, 280(19): 18558-18561. DOI: 10.1074/jbc.c500089200.

BORDT E A CLERC P ROELOFS B A The putative Drp1 inhibitor mdivi-1 is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species Dev Cell 2017 40 6 583 594 10.1016/j.devcel.2017.02.020 BORDT E A, CLERC P, ROELOFS B A, et al . The putative Drp1 inhibitor mdivi-1 is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species[J ] . Dev Cell, 2017, 40(6): 583-594. e6. DOI: 10.1016/j.devcel.2017.02.020.

TÁBARA L C POVEDA J MARTIN-CLEARY C Mitochondria-targeted therapies for acute kidney injury Expert Rev Mol Med 2014 16 e13 10.1017/erm.2014.14 TÁBARA L C, POVEDA J, MARTIN-CLEARY C, et al . Mitochondria-targeted therapies for acute kidney injury[J ] . Expert Rev Mol Med, 2014, 16: e13. DOI: 10.1017/erm.2014.14.

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