川芎嗪联合依达拉奉对脓毒血症大鼠自由基及细胞因子的影响

Effects of ligustrazine and edaravone on free radicals and cytokines in rats with sepsis

目的:观察川芎嗪联合依达拉奉(ED)对脓毒血症大鼠自由基及细胞因子的影响。方法:40只SD大鼠随机分为假手术组、手术对照组、川芎嗪治疗组、川芎嗪联合ED治疗组(联合治疗组),手术对照组和两治疗组均予盲肠结扎穿刺法制作大鼠脓毒血症模型,术前15min及术后3h各皮下注射乳酸左氧氟沙星20mg/kg,川芎嗪治疗组于术前15min及术后3h各皮下注射川芎嗪15mg/kg,联合治疗组于术前15min及术后3h各联合皮下注射ED5mg/kg和川芎嗪15mg/kg。各组均于术后18h采血测羟自由基(·OH)、肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)、白介素-6(IL-6),取肝组织进行光镜、电镜检查及·OH检测。结果:手术对照组大鼠肝组织显微镜下可见肝细胞浊肿、水样变,电镜下可见肝细胞核轻度固缩,内质网扩张,两治疗组大鼠肝组织病变明显改善。手术对照组血和肝组织·OH活力及血TNF-α、IL-6浓度与假手术组比较明显升高(P<0.01)。川芎嗪治疗组血·OH活力、TNF-α、IL-6浓度及联合治疗组血·OH活力与手术对照组比较明显降低(P<0.05)。川芎嗪治疗组肝组织·OH活力及联合治疗组血TNF-α、IL-6浓度和肝组织·OH活力与手术对照组比较明显降低(P<0.05或P<0.01)。联合治疗组与川芎嗪治疗组间血·OH活力及TNF-α、IL-6浓度比较差异无显著性(P>0.05)。联合治疗组肝组织·OH活力与川芎嗪治疗组比较明显降低(P<0.01)。4组间IL-2浓度比较差异无显著性(P>0.05)。结论:川芎嗪联合ED能降低脓毒血症大鼠血和肝组织·OH活力及血TNF-α、IL-6浓度,有抑制炎症反应和保护肝功能的作用,值得临床推荐使用。

Objective To observe the effects of ligustrazine and edaravone on free radicals and cytokines in rats with sepsis. Methods 40 Sprague-Dawley rats were randomly divided into 4 groups, sham operation group （group A）, controlled operation group （group B）, ligustrazine group （group C）, ligustrazine and edaravone group （group D）. Rats in group B, C, D were made as sepsis models through appendix ligation and puncture, and received subcutaneous injection of 20 mg/kg lactate levofloxacin 15 min before and 3 h after operation. Accompanied with lactate levofloxacin, 15 mg/kg ligustrazine was used in group C, and 15 mg/kg ligustrazine plus 5 mg/kg edaravone were used in group D. Blood and liver were taken from rats in all groups 18 h after operation. The activity of hydroxyl radical （·OH） in blood and liver was detected, and the concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-2 （IL-2）, and interleukin-6 （IL-6） in blood were detected. Pathological changes of liver were observed by microscope and electron microscope. Results Cloudy swelling, pyknosis, and extension of endoplasmic reticulum in hepatocytes were observed in microscope and electron microscope in group B. There were on obvious pathological changes in group C and group D. The activity of ·OH in blood and liver, and the concentrations of TNF-α and IL-6 in blood were significantly higher in group B than in group A （P 〈 0.01 ）, and were significantly lower in group C and group D than in group B （P 〈 0.05 or P 〈 0.01 ）. There were no significant differences of ·OH activity and TNF-α and IL-6 concentrations in blood between group C and group D （P 〉 0.05）. The activity of .OH in liver in group D was significantly lower than that in group C （P〈 0.01）. There were no significant differences of IL-2 concentration in blood among the four groups （P 〉 0.05）. Conclusion The activity of ·OH in blood and liver, and the concentrations of TNF-α and IL-6 in blood were decreased in rats with sepsis after being treated by ligustrazine and edaravone, which can suppress inflammatory reaction and protect hepatic function.