Horton J W, White D J, Maass D L, Hybki D P, Haudek S, Giroir B
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Trauma. 2001 Mar;50(3):397-406; discussion 407-8. doi: 10.1097/00005373-200103000-00002.
This study examined the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-kappa B (NF-kappaB) nuclear translocation, on secretion of inflammatory cytokines by cardiac myocytes, and on cardiac function after major burn trauma.
Adult rats were divided into four experimental groups: group I, shams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 hours before and immediately after burn); group III, burns (third-degree scald burn over 40% total body surface area) given lactated Ringer's solution (4 mL/kg/% burn); and group IV, burns given lactated Ringer's solution plus vitamins as described above. Hearts were collected 4, 8, 12, and 24 hours after burn to assay for NF-kappaB nuclear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-alpha secretion by cardiomyocytes.
Compared with shams, left ventricular pressure was lower in burns given lactated Ringer's solution (group III) (88 +/- 3 vs. 64 +/- 5 mm Hg, p < 0.01) as was +dP/dt max (2,190 +/- 30 vs. 1,321 +/- 122 mm Hg/s) and -dP/dt max (1,775 +/- 71 vs. 999 +/- 96 mm Hg, p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-kappaB nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by 24 hours after burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and +/-dP/dt (82 +/- 2 mm Hg, 1,880 +/- 44 mm Hg, and 1,570 +/- 46 mm Hg/s) comparable to those measured in shams. Antioxidant vitamins in burns inhibited NF-kappaB nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes.
These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-kappaB and interrupting cardiac inflammatory cytokine secretion.
本研究探讨了抗氧化维生素A、C和E对核转录因子-κB（NF-κB）核转位、心肌细胞炎性细胞因子分泌以及严重烧伤创伤后心脏功能的影响。
成年大鼠分为四个实验组：第一组，假手术组；第二组，假手术组在烧伤前24小时及烧伤后立即口服抗氧化维生素（维生素C，38mg/kg；维生素E，27U/kg；维生素A，41U/kg）；第三组，烧伤组（全身40%体表面积三度烫伤）给予乳酸林格氏液（4mL/kg/%烧伤面积）；第四组，烧伤组给予乳酸林格氏液加上述维生素。在烧伤后4、8、12和24小时采集心脏，检测NF-κB核转位，在烧伤后24小时采集心脏，检测心脏收缩功能或心肌细胞肿瘤坏死因子-α分泌。
与假手术组相比，给予乳酸林格氏液的烧伤组（第三组）左心室压力较低（88±3 vs. 64±5mmHg，p<0.01），+dP/dt max（2,190±30 vs. 1,321±122mmHg/s）和 -dP/dt max（1,775±71 vs. 999±96mmHg，p<0.01）也较低。未接受维生素治疗的烧伤组（第三组）在烧伤后4小时出现心脏NF-κB核迁移，在烧伤后24小时出现心肌细胞分泌肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6。烧伤组的抗氧化治疗（第四组）改善了心脏功能，产生的左心室压力和±dP/dt（82±2mmHg，1,880±44mmHg，和1,570±46mmHg/s）与假手术组测得的结果相当。烧伤组中的抗氧化维生素在烧伤后的所有时间均抑制NF-κB核迁移，并减少烧伤介导的心肌细胞细胞因子分泌。
这些数据表明，烧伤创伤中的抗氧化维生素治疗至少部分通过抑制转录因子NF-κB的转位和中断心脏炎性细胞因子分泌来提供心脏保护。
