Dexmedetomidine intervention effects on aquaporin -1 and inflammatory cytokines in myocardial tissue of septic rat / 中国中西医结合急救杂志

ABSTRACT

Objective To study the regulation of aquaporin-1(AQP-1)changes in the heart of septic rats, compare the correlations of the AQP-1 with myocardial cytokines tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6),and myocardial tissue water content,and to investigate the dexmedetomidine protective effect on myocardia in septic rats and its possible mechanism. Methods According to the random number table methods,90 male Sprague-Dawley(SD)rats were divided into sham operation group,sepsis model group and dexmedetomidine group, 30 rats in each group. The rat sepsis model was established by cecal ligation and puncture(CLP). In the sham operation group,the animal abdomen was only opened and closed without CLP. Half hour before operation in dexmedetomidine group,dexmedetomidine 1μg/kg(2μg/mL)was injected into the vein,while in the model and sham groups,saline 5 mL/kg was subcutaneously injected into the rat after the operation. At 2,12,24,48,72 hours after operation,6 rats were sacrificed and their hearts removed at one time point in a group. Enzyme linked immunosorbent assay(ELISA)was used to detect the content of AQP-1 and the levels of the TNF-α,IL-6 in the myocardial tissue homogenate at all time points,the myocardial tissue water content was detected by dry wet weight,and the correlations between AQP-1 and TNF-α,IL-6 and between AQP-1 and myocardial tissue water content were compared. Results From 2 hours after operation,the levels of the AQP-1,TNF-αand IL-6 in model group were significantly higher than those in the sham operation group;with prolongation of time,the level of AQP-1 and myocardial tissue water content were decreased, but the levels of TNF-α and IL-6 were persistently increased. From 2 hours after operation in dexmedetomidine group,all the above indexes except myocardial tissue water content at 72 hours after operation were significantly lower than those in the model group〔AQP-1(ng/g)9.29±0.15 vs. 9.73±0.26,TNF-α(pg/g)109.47±8.41 vs. 128.13±7.36,IL-6(pg/g)232.95±20.56 vs. 279.71±22.24,myocardial tissue water content(74.82±6.37)%vs.(75.62±6.39)%,all P<0.05〕,but still higher than those of the sham operation group. The correlation analyses for the septic group showed that the change of AQP-1 was positively correlated to the myocardial water content in early stage(r=0.418,P=0.001)and later stage(r=0.235,P=0.022),and the changes of the AQP-1 in early stage (at post-operative 2 hours)were positively correlated to the concentration changes of the cytokines TNF-α(r=0.235,P=0.021)and IL-6(r=0.345,P=0.003),but in the later stage(at post-operative 72 hours)were negatively correlated with the changes of TNF-α(r=-0.408,P=0.037)and IL-6(r=-0.276,P=0.002). Conclusions In the early stage of septic rats,there is obvious myocardial injury,resulting in the over expression of AQP-1 and the occurrence of myocardial edema,dexmedetomidine can play a role in myocardial protection in such rats and its mechanism is possibly related to the reduction of the expression of AQP-1 and the levels of inflammatory cytokines, and in turn the alleviation of myocardial cell edema.