右美托咪啶抑制NF-κB活化减轻肢体缺血再灌注损伤的研究

Dexmedetomidine reduces ischemia- reperfusion injury in skeletal muscle via suppressing activation of NF-κB

目的探讨右美托咪啶预处理对抑制NF-κB活化及减轻肢体缺血再灌注损伤的影响及机制。方法将21只成年雄性SD大鼠按随机数字表法分为假手术组(Sham组)、缺血再灌注组(I/R组)、缺血再灌注+右美托咪啶预处理组(DEX组),每组各7只。DEX组在麻醉后腹腔注射右美托咪啶25μg/kg,其余两组给予相应体积的0.9%氯化钠溶液,30min后单侧股部切口,无创动脉夹夹闭股动脉,用橡皮筋以恒定张力结扎该侧肢体,Sham组仅行股部手术、分离股动脉不夹闭,其余两组缺血3h后去除动脉夹及橡皮筋。采用ELISA法检测血清IL-1、IL-6、TNF-α,Western blot检测胞核NF-κB,光镜观察腓肠肌形态,并测定湿/干重比值。结果显微镜下可见Sham组大鼠腓肠肌肌纤维排列整齐、间质少有炎性细胞浸润,I/R组大鼠腓肠肌肌纤维排列紊乱并出现明显水肿、间质中出现大量炎症细胞,DEX组大鼠腓肠肌肌纤维排列欠规则、间质中有少量炎性细胞,但较I/R组有所好转。与Sham组相比,I/R组湿/干重比值、IL-1、IL-6、TNF-α、NF-κB水平均明显升高(均P<0.05);与I/R组相比,DEX组湿/干重比值、IL-1、IL-6、TNF-α、NF-κB水平均明显降低(均P<0.05)。结论右美托咪啶可抑制NF-κB信号通路活化,减轻肢体缺血再灌注损伤。

Objective To investigate the effect of dexmedetomidine （DEX） on skeletal muscle injury induced by ischemia- reperfusion and related mechanisms. Methods Twenty- one SD rats were randomly divided into sham- operated group （sham group）, ischemia- reperfusion （I/R） group and I/R＋ DEX group. In DEX group, DEX （25μg/kg） was injected after anesthesia;while in the other groups, the same volume of saline was also injected. After 30 minutes, the hind limb ischemia was induced by clamping the common femoral artery and ligating collateral circulation. After 3h of ischemia, the clamp and tourniquet were removed and the rats underwent reperfusion for 2h. The plasma concentrations of IL- 1, IL- 6 and TNF- α were measured with enzyme- linked immunosorbent assay. The gastrocnemius muscle was harvested, the expression of NF- κB protein was detected by Western blot; the morphological changes were observed with HE staining; the wet/dry ratio was also measured. Results The intact muscle fiber and few inflammatory cel s infiltration in interstitial space were observed with light microscopy in sham group. Disordered arrangement and edema of muscle fibers and interstitial inflammatory cells infiltration were showed in I/R group. In DEX group, the disordered arrangement of muscle fiber and infiltration of inflammatory cel s in the stroma were attenuated as compared to I/R group. The wet/dry ratio, plasma levels of TNF- αand NF- κB were higher in I/R group than those in sham group （P＆lt;0.05）. The wet/dry, plasma IL- 1, IL- 6, TNF- αlevels and NF- κB expression were significantly lower in DEX group than those in I/R group （P＆lt;0.05）. Conclusion Dexmedetomidine can reduce the ischemia- reperfusion injury of skeletal muscle, which is associated with the inhibition of NF- κB activation.