ABSTRACT
BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Subject(s)
Rats , Male , Animals , Myocardial Reperfusion Injury/metabolism , Connexin 43/genetics , Sumoylation , Down-Regulation , Rats, Sprague-Dawley , Arrhythmias, Cardiac/drug therapy , Myocardial Ischemia/metabolism , RNA, Small Interfering/metabolismABSTRACT
As a new laboratory test for evaluation of endogenous pain inhibition,conditioned pain modulation (CPM) deficiency means dysfunction of endogenous pain inhibitory systems and higher incidence of chronic pain.Age,psychological factors and physical activity all seem to influence the individual CPM effect.A standard CPM testing way has an important role in comparison between different researches.
ABSTRACT
Objective A rat model of chronic post-thoracotomy pain is used to study whether acute pain and pre-operative diffused noxious inhibitory controls(DNIC) can predict chronic pain and how DNIC changes when pain maintains.Methods Rats were randomly divided into three groups:naive group,sham group and model group.DNIC was constantly assessed in individual rats,along with each animal's mechanical hyperalgesia and cold allodynia after thoracotomy.Results In model group,the incidence of chronic post-thoracotomy pain was 55%(11 of 20),which was named CPTP group,and the other 9 rats without chronic pain was defined as non-CPTP group.The pre-operative DNIC was significantly weaker in CPTP group with lower mechanical threshold on 6 days after surgery and higher cold sensitivity on 6 days after surgery comparing with non-CPTP group.In the acute pain phase (day 3),DNIC was decreased in both CPTP group and non-CPTP group as compared with pre-operative period.Besides,DNIC was recovered in non-CPTP group while kept impaired in CPTP group on 21 days after surgery.Conclusions Pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP.DNIC was decreased both in acute pain and chronic state,while returned to normal when pain sense was normal.