Changes of different connexins and mitochondrial dynamins in early acute kidney injury after liver transplantation

Abstract

Objective To explore the potential relationship between different connexins and mitochondrial dynamic imbalance and mitochondrial injury in early acute kidney injury after liver transplantation. Methods 24 healthy specific pathogen-free （SPF） SD male rats were randomly divided into the sham operation group （sham group， n = 6）， and 2-， 4- and 8-h reperfusion liver transplantation groups （M2， M4 and M8 groups， n = 6 each）. In the sham group， open surgery alone was performed for vessel separation. In the M2， M4 and M8 groups， orthotopic liver transplantation was conducted. Renal function and renal pathological examination were determined. The expression levels of connexin 32 （Cx32）， Cx43， dynamin-related protein 1 （Drp1）， mitofusin-1 （Mfn1）， Mfn2， optic atrophy 1 （Opa1） and C/EBP homologous protein （CHOP）， an endoplasmic reticulum stress-related protein， were detected in each group. The morphological changes of mitochondria were observed under electron microscope. Results Compared with the sham group， the pathological score of kidney tissue injury in the M2 group was increased （P < 0.01）， and gradually increased over reperfusion time， and reached the peak in the M8 group （P < 0.001）. However， serum creatinine （SCr） and blood urea nitrogen （BUN） levels were up-regulated only in the M8 group （P < 0.001， P < 0.05）. Compared with the sham group， Cx32 level was increased in the M2 group （P < 0.01）， Cx43 level was increased in the M4 group （P < 0.001）， and reached the peak in the M8 group （both P < 0.001）. Compared with the sham group， the expression levels of Drp1， Mfn1， Mfn2 and OPA1 were up-regulated in the M2 group （all P < 0.001）. Under electron microscope， mitochondrial injury， mitochondrial autophagy， lysosomal autophagy and slightly swollen rough endoplasmic reticulum were observed in the M2 group. The degree of mitochondrial injury was aggravated over reperfusion time during liver transplantation. Mitochondrial autophagy and endoplasmic reticulum - mitochondria contact sites were observed in the M2， M4 and M8 groups. Conclusions Kidney pathological injury and mitochondrial injury occur early after autogenous orthotopic liver transplantation in SD rats. The diagnosis of kidney injury by SCr and BUN levels can be delayed. The expression level of Cx32 in the renal tissues is up-regulated early after liver transplantation. Active mitochondrial division and fusion can be seen， suggesting that the transmission of injury signals by Cx32 is associated with mitochondrial injury and mitochondrial dynamic imbalance， which may be an important mechanism of early acute kidney injury after liver transplantation.

Keywords

• |acute kidney injury|liver transplantation|connexin|mitochondrial dynamics