Research Article: The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 431

Date Published: December 13, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Alexandre Maximiliano Trevisan, Bruno Cogliati, Adriana Ribeiro Homem, Thiago Pinheiro Arrais Aloiav, Nelson de Aquino, Jairo Marques Moreira, Leonardo da Cruz Reno, Alexandre Moulin Naumann, Flavio Henrique Ferreira Galvão, Wellington Andraus, Luiz Augusto Carneiro D’Albuquerque.


To evaluate that Connexin (Cx43) plays a role in lesions after hepatic
ischemia/reperfusion (IR) injury.

We use Cx43 deficient model (heterozygotes mice) and compared to a wild
group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The
heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes
(AST, ALT, GGT) and histology.

The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Partial Text

The number of liver surgeries such as transplantation and resection has increased
exponentially over recent decades. During surgical processes, it is important to
control bleeding through the complete or partial impediment of blood flow to the
liver1. This procedure leads to oxygen deprivation in the remaining tissue, causing
tissue injury2.

A total of 34 mice, 16 genetically modified, deficient in one of the alleles of
Cx43+/-, and 18 wild mice C57 BL/6(Cx43+/+). All had the
genotype PCR for the gene Cx43. All were male, adult (8 weeks), weight +/- 30g.

In the evaluation of the hepatic lesion after IR, through the measurement of Alamine
transaminase (ALT), the group Knockout heterezigoto, that is, with lower expression
of Cx43, showed values significantly higher, when compared with the wild control
group (Fig. 5).

To our knowledge, this is the first study that demonstrated a worse response to I/R
injury in animals with Cx 43 deficiency.

The deficiency of Cx 43 worses the ischemia/reperfusion injury in an experimental
model using heterozygote mice for the expression of this conexin.




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