| Background:QTc interval prolongation induced by droperidol is associated with potential Torsades de pointes(TdP), which is a severe arrhythmia with mortality for patients. Connexin43 (Cx43) protein was involved in QTc interval prolongation, and electro-acupuncture(EA) at Neiguan acupiont was reported with anti-arrhythmic property.Objective:The present study was to determine the hypothesis that EA at Neiguan acupiont may abbreviate QTc interval prolongation induced by droperidol via increasing Cx43 mRNA and protein expression in Sprague-Dawley rats.Methods:The rats were divided into groups including C(controlled group), DL(low dose droperidol group), DH(high dose droperidol group), EC(EA group), EDL(EA combined low dose droperidol group) and EDH(EA combined high dose droperidol group). There were 8 rats in each group. EC, EDL and EDH groups were pre-punctured at left Neiguan acupiont and the electrically stimulated with dense-sparse pulses, frequency of 2-10-100 Hz, and 1mA strength. Then, DL and EDL groups were injected with droperidol 0.13mg/kg through femoral vein; DH and EDH groups were injected with droperidol 1.3mg/kg through femoral vein. C and EC groups were injected with normal saline at the same volume. Electrocardiograms (ECG) were recorded in Lead II on the electrocardiogram (ECG) at Omin before injection,5min, 10min,15min,30min,60min and 120min after injection. QTc intervals were calculated with Bazett’s formula QTc-B=QT/V(RR). Cx43 mRNA expression was measured by RT-PCR and Cx43 protein was measured by western blotting in ventricular muscles of rats. Immunohistochemical localization were analyzed for Cx43 protein distribution and expression in the ventricular muscle tissues.Results:(1)The effect of Neiguan EA on the QTc interval in rats treated with Droperidol.①Compared with control group, QTc intervals in DL group significantly prolonged at 5min, 10min,15min and 30min(P<0.01); Compared with control group, QTc intervals in DH group significantly prolonged QTc intervals at 5min, 10min, 15min,30min,60min and 120min(P<0.01).②Compared with DL group, QTc intervals in EDL group significantly shorten at 5min(P<0.01),10min(P<0.05), 15min(P<0.01) and 30min(P<0.05).③Compared with DH group, QTc intervals in EDH group significantly shorten at 5min(P<0.05),10min(P<0.01),15min (P<0.01),30min(P<0.01) and 60min(P<0.01). ④There was no significant difference about QTc intervals between C group and EC group. (2)Cx43 mRNA levels were significantly up-regulated in EC group (0.92±0.03), and P<0.05 compared with C group (0.84±0.02); Cx43 mRNA levels were significantly up-regulated in EDL group (0.91±0.03), and P<0.05 compared with DL group(0.84±0.02); Cx43 mRNA levels were significantly up-regulated in EDH group (0.73±0.02), and P<0.05 compared with DH group(0.64±0.03). (3)Cx43 protein levels were significantly up-regulated in EC group(1.46±0.15), and P<0.01 compared with C group (1.09±0.08); Cx43 protein levels were significantly up-regulated in EDL group (1.57±0.16), and P＜0.01 compared with DL group (1.09±0.10); Cx43 protein levels were significantly up-regulated in EDH group (1.15±0.05), and P<0.01 compared with DH group (0.96±0.08). (4) Immunohistochemistry method was used to examine the distribution and mean density of Cx43 protein in different groups. (Din C and DL groups, Cx43 proteins extensively localized at ventricular cell-cell contacts and intercalated disk with pointlike distribution in dark brown color; In DH group, Cx43 proteins localized at ventricular cell-cell contacts and intercalated disk with pointlike distribution in slight brown color; In EC group, Cx43 proteins extensively localized at ventricular cell-cell contacts and intercalated disk with darker and elongated linear distribution; In EDL group, Cx43 proteins localized at ventricular cell-cell contacts and intercalated disk with pointlike distribution in dark brown color; In EDH group, Cx43 proteins localized at ventricular cell-cell contacts and intercalated disk with pointlike distribution in dark brown color. (2)The mean density of Cx43 proteins was 0.189±.008 in EC goup, P＜0.01 compared with 0.168±0.009 in C goup, and there were significant difference in the two groups; The mean density of Cx43 proteins was 0.202±.009 in EDL goup, P＜0.01 compared with 0.160±0.009 in DL goup, and there were significant difference in the two groups; The mean density of Cx43 proteins was 0.198±0.009 in EDH goup, P<0.01 compared with 0.153±0.007 in DL goup, and there were significant difference in the two groups.Conclusion:Droperidol significantly prolonged QTc intervals with a dose dependent manner. Neiguan EA significantly abbreviated the QTc intervals prolongation induced by droperidol by increasing Cx43 mRNA and protein expression. |
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