Effects of dexmedetomidine on brain injury and long -term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion
10.3760/cma.j.issn.1671-8925.2019.02.003
- VernacularTitle:右美托咪定对大鼠原位移植肝脏缺血再灌注后脑损伤及远期认知功能障碍的影响
- Author:
Hongjie LYU
1
;
Lijuan DONG
;
Hongjun LI
Author Information
1. 郑州人民医院麻醉科 450002
- Keywords:
Dexmedetomidine;
Liver transplantation;
Ischemia/reperfusion;
Cognitive function;
Aquaporin 4;
Protein kinase C
- From:
Chinese Journal of Neuromedicine
2019;18(2):122-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of dexmedetomidine (DEX) on brain injury and long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion and its mechanism. Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into sham-operated group (n=18), orthotopic liver transplantation ischemia/reperfusion group (I/R group, n=18) and DEX pre-administration group (DEX group, n=18). The orthotopic liver transplantation ischemia/reperfusion models were established in I/R group and DEX group. Rats of the DEX group were intraperitoneally injected with DEX 100 μg/kg 30 min before the incision, and an equal volume of normal saline was injected into rats of the sham-operated group and I/R group at the same time. Twelve rats in each group were sacrificed 3 d after operation and brain tissues were taken. The pathological changes of the hippocampus were observed under light microscope. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis index of the hippocampus. Western blotting was used to detect the protein levels of aquaporin 4 (AQP4) and protein kinase C (PKC) in the hippocampus. The remaining 6 rats accepted Morris water maze test to evaluate the long-term cognitive function 30 d after surgery. Results As compared with those in the sham-operated group, rats in the I/R group and DEX group had hippocampus edema and disordered cell arrangement; as compared with sham-operated group, I/R group and DEX group had significantly increased neuronal apoptosis index, significantly increased protein levels of AQP4 and PKC, significantly shorter quadrant retention time of the platform, and statistically longer escape latency (P<0.05). As compared with those in the I/R group, the pathological damage of hippocampal neurons was significantly alleviated, the neuronal apoptosis index was significantly decreased, the protein levels of AQP4 and PKC were statistically decreased, and the residence time of the quadrant in the platform was significantly prolonged, and the escape latency was statistically shorter in DEX group (P<0.05). Conclusion Pre-administration of DEX may reduce the brain damage and improve long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion, which may be related to down-regulating the AQP4 and PKC expression levels and reducing neuronal apoptosis.
