Dexmedetomidine Reduce Multiple Organ Injury Induced by Lung Ischemia/ Reperfusion of Mice Through Inhibiting Endoplasmic Reticulum Stress Response

Abstract

To investigate the effect of Dexmedetomidine reduce brain, myocardium and kidney injury induced by lung ischemia/reperfusion of mice through inhibiting endoplasmic reticulum stress response. SPF C57BL/6J male mice were randomly divided into 5 groups (n = 10): the sham operation group (group sham), the ischemia reperfusion Group (Group I/R), the Atipamezole Group (Group Atip), dexmedetomidine Group (Group-DEX) and dexmedetomidine+AtipamezoleGroup (Group DA). Lung ischemia reperfusion models were established with the method of 30min in-vivo left hilus occlusion followed by 180min reperfusion. In addition to the steps same as Group I/R, the mice in Groups Atip, Dex and DA were given Atip(250μg/kg), Dex(20μg/kg), and Dex+ Atip(20μg/kg+250μg/kg) respectively by intraperitoneal injection 30min before hilar occlusion. After reperfusion, the blood was taken from the eye-orbit to determine the activity of serum CK-MB and LDH and the levels of serum creatinine and urea nitrogen. The brain tissue was taken to determine the brain water content. The tissue of myocardium, brain and kidney was taken to observe the cellular morphology change under the light microscope. The expression of Caspase3 activity in heart, brain and kidney was determined with Thermos Scientific Microplate Reader. The TUNEL method was used to detect the apoptotic index of heart, brain and kidney. The Western blot and RT-PCR were used to determine the expression of proteins and mRNA of JNK, Caspase12, CHOP and GRP78. Compared with Group Sham, obvious injury in the tissue of myocardium, brain and kidney was observed in the other four groups under the light microscope. The activity of CKMB and LDH, and the levels of serum creatinine, urea nitrogen and brain water content were significantly increased as well. The apoptotic index, Caspase3 activity, and the expression of the proteins and mRNA of JNK, Caspase12, CHOP and GRP78 were also significantly elevated. Compared with Group I/R, Atip and DA, the mitigated injury in the myocardium, brain and kidney was observed in Group DEX under the light microscope. The activity of CK-MB and LDH, and the levels of serum creatinine, urea nitrogen and brain water content were decreased and the apoptotic index, Caspase3 activity, and the expression of the proteins and mRNAs of JNK, Caspase12 and CHOP were also significantly decreased in Group DEX, but the proteins and mRNA expression of GRP78 were significantly elevated. For the comparison among theGroup I/R, Atip and DA, there is no significant difference was found.(grp78).The pre-administration of DEX can mitigate the heart, brain and kidney injury induced by lung ischemia reperfusion. The mechanism may be related to the activation of α2-adrenergic receptor and inhibition of endoplasmic reticulum over-response.