RESUMO
Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in morphine-or sufentanil-induced inhibition of arrhythmia induced by myocardial ischemia-reperfusion (I/R) in rats and the relationship with connexin43 (Cx43).Methods Forty-eight healthy SPF adult male Sprague-Dawley rats,weighing 200-300 g,were randomly divided into 6 groups (n=8 each) using a random number table:sham operation group (group S);I/R group;morphine group (group M);sufentanil group (group Suf);morphine + ERK inhibitor PD98059 group (group MP);sufentanil + PD98059 group (group SP).Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery,followed by reperfusion.In M and Suf groups,the animals were subjected to three cycles of 5-minute drug infusion (morphine 0.3 mg/kg and sufentanil 3 μg/kg,respectively) via the femoral vein interspersed with 5-minute drug-free periods starting from the time point immediately before ischemia.PD98059 10 mg/kg was injected intravenously at 10 min before ischemia in MP and SP groups.The development of ventricular arrhythmia was recorded within 30 min of ischemia and 30 min of reperfusion,and the arrhythmia was scored (AS).The animals were then sacrificed at 120 min of reperfusion,and the myocardial specimens were obtained for determination of the expression of total Cx43 (t-Cx43),phosphorylated Cx43 (p-Cx43),and phosphorylated ERK (p-ERK) by Western blot.Results Compared with group S,the AS was significantly increased,and the expression of p-Cx43 was significantly down-regulated in the other groups,and the expression of t-Cx43 and p-ERK was significantly down-regulated in I/R,SP and MP groups (P＜0.05).Compared with group I/R,the AS was significantly decreased,and the expression of t-Cx43,p-Cx43 and p-ERK was significantly up-regulated in M and Suf groups (P ＜ 0.05).Compared with M and Suf groups,the AS was significantly increased,and the expression of t-Cx43 and p-Cx43 was significantly down-regulated in SP and MP groups (P ＜ 0.05).Conclusion The mechanism by which morphine or sufentanil inhibits arrhythmia induced by myocardial I/R is associated with up-regulated expression of myocardial Cx43 after activation of ERK signaling pathway in rats.
RESUMO
Objective To investigate the effect of liver cirrhosis on the potency of propofol for sedation in rats. Methods Fifty-eight male SD rats, aged 10-12 weeks, weighing 180-220 g, were randomly divided into 3 groups: control group (group C, n = 18), mild liver cirrhosis group (group M1, n =20) and severe liver cirrhosis group (group M2, n = 20). The model of liver cirrhosis was established using four factors described by Chen et al. After successful establishment of the model, propofol was injected intravenously. The dose of propofol was determined by up-and-down sequential method for loss of righting reflex. The dose of propofol was 5.912 mg/kg in the first rat and the ratio of the doses between the two consecutive rats was 0.85. ED50 of propofol was calculated using up-and-down sequential method. Results ED50 of propofol was significantly lower in group M1 and M2 than in group C and in group M2 than in group M1 ( P ＜ 0.05 or 0.01 ). Conclusion The liver cirrhosis can enhance the potency of propofol for sedation in rats.
