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.

Objective The study was to compare the effect of sufentanil and morphine preconditioning on ischemia /reperfusion-induced ventricular arrhythmias and the expression and distribution of myocardial Cx43 in rats.The regulation mechanisms that how sufentail and morphine lead to the change of Cx43 were also studied.Methods 32 male SD rats were randomly divided into 4 groups:sham operation group (group C),ischemia/reperfusion (group I/R),morphine preconditioning group(group M) and sufentanil preconditioning group(group S),each group had 8 rats.Established myocardial ischemia/reperfusion model,continuous recorded Ⅱ ECG,mean arterial pressure(MAP) and heart rate(HR).The ventricular arrhythmias at the 30 min before reperfusion was observed and the ventricular arrhythmias score of each group was calculated by ECG analysis; expression and distribution of Cx43 protein were observed by immunohistochemical technique.Results Compared with group C,the HR,MAP,RPP of group I/R were decreased obviously (P ＜ 0.05),while the arrhythmia score was significantly higher(P ＜ 0.05).Compared with group I/R,the extent of the declined of HR,MAP,RPP of group M and group S were eased significantly(P ＜ 0.05) and arrhythmia score was significantly lower(P ＜ 0.05).The HR,MAP,RPP of group M and group S are closer(P ＞ 0.05).Compared with the group C,Cx43 expression level in group I/R was significantly reduced (P ＜ 0.05) and the distribution was disordered,while compared with the group I/R,Cx43 expression level in group M and group S were significantly increased (P ＜ 0.05),and its distribution was structured.In group M and group S,Cx43 expression level were closer(P ＞ 0.05) and so as their distribution.Conclusion Sufentanil and morphine could inhibit the reduction of myocardial Cx43 expression level and improve its distribution which could played an important role in anti-arrhythmic during ischemia-reperfusion.

Objective To observe the protective effect of electroacupuncture(EA)on ankle joint synovitis and HIF-1 α/MDM2/p53 signaling pathway in adjuvant arthritis(AA)rats.Methods SD rats were randomly divided into control group,model group,sham EA group,agonist group,EA group,EA+antagonist group,antagonist group,with 10 rats in each group.Preparation of AA rat model by injecting Freund's complete adjuvant into bilateral foot pads of rats.EA(2 Hz,3 V)was applied to bilateral ST36 and GB39 or two control points(5 mm left to ST36 and GB39)for 15 min,once every other day for a total of 8 times.HIF-1 α agonists and antagonists were injected into the tail vein of rats in the corresponding groups.The inflammatory conditions of the ankle joint were observed by HE staining,and the contents of serum HIF-1 α was assayed by ELISA.mRNA expression of HIF-1α,VEGF,MDM2 and p53 were detected by RT-PCR,protein expression of HIF-1α,VEGF,MDM2 and p53 were detected by Western blot in synovium of AA rats.Results The results of HE staining showed that compared with the control group,the synovial cells in the model group had significant proliferation and inflammatory cell infiltration(P<0.01);Compared with the model group,the arthritic reaction of the rats in the EA group,the EA+antagonist group and the antagonist group was significantly reduced(P<0.01),while the arthritic reaction of the rats in the sham EA group and the agonist group was still serious(P>0.05).The results of ELISA showed that compared with the control group,the serum HIF-1αexpression of the model group rats was significantly increased(P<0.01);Compared with model group,serum HIF-1αexpression of rats in EA group,EA+ antagonist group and antagonist group was significantly decreased(P<0.01);There was no significant difference in serum HIF-1αexpression among the model group,sham EA group and agonist group(P>0.05).RT-PCR results showed that compared with the control group,the mRNA expression of HIF-1α,VEGF,MDM2 and p53 of model group rats increased significantly;Compared with model group,the mRNA expression of HIF-1α,VEGF and MDM2 of rats in EA group,EA+antagonist group and antagonist group decreased significantly,while the mRNA expression of p53 increased significantly.Western blot results showed that compared with the control group,the protein expression of HIF-1α,VEGF,MDM2 and p53 of model group rats increased significantly;Compared with model group,the mRNA expression of HIF-1α,VEGF and MDM2 of rats in EA group,EA+antagonist group and antagonist group decreased significantly,while the mRNA expression of p53 increased significantly.Conclusion Electroacupuncture intervention has significant protective effect on ankle inflammation in AA rats,HIF-1 α/MDM2/p53 signaling pathway plays a key role in this process.