肿瘤坏死因子-α单抗对烫伤大鼠组织脂多糖结合蛋白mRNA表达的影响

Effect of TNF α monoclonal antibody on tissue lipopolysaccharide binding protein mRNA expression in rats after thermal injury

目的探讨肿瘤坏死因子α（ＴＮＦα）单抗治疗对烫伤后组织ＴＮＦα及脂多糖结合蛋白（ＬＢＰ）ｍＲＮＡ表达、不同器官功能改变的影响。方法采用大鼠３５％体表面积Ⅲ度烫伤模型，检测伤后肺、肝、肠、肾等组织ＴＮＦα及ＬＢＰｍＲＮＡ水平。结果烫伤后肺、肝、肠、肾等组织ＴＮＦα及ＬＢＰｍＲＮＡ表达较伤前水平均有显著升高（Ｐ＜００５～００１），约为正常对照的１７～２５倍。给予ＴＮＦα单抗治疗后可显著降低肺、肠、肾组织ＴＮＦαｍＲＮＡ的表达（Ｐ＜００５～００１），但对肝组织表达量无显著影响（Ｐ＞００５）；同时，组织ＬＢＰｍＲＮＡ的表达亦显著下降（Ｐ＜００５～００１），约为烫伤组的３６０％～７２９％，其中肺、肠、肾组织基本恢复至正常水平。烫伤后反映多个器官功能改变的生化指标如谷丙转氨酶、总胆红素、尿素氮、乳酸脱氢酶、心型肌酸激酶同工酶等均较伤前显著升高（Ｐ＜００１），ＴＮＦα单抗治疗可不同程度地减轻多个器官功能损害。结论严重烧伤后ＴＮＦα可显著影响不同组织ＬＢＰｍＲＮＡ的表达及多个器官的功能。及早应用ＴＮＦα抗体能有效防治创伤后多器官损害，其作用机理与抑制多种组织ＬＢＰｍＲＮＡ表达密切?

Objective To explore the effects of tumor necrosis factor α (TNF α) monoclonal antibody (MAb) on tissue TNF α and lipopolysaccharide binding protein (LBP) mRNA expression, and multipleorgan dysfunction in rats after thermal injury. Method 24 male Wistar rats were subjected to a 35 % total body surface area full thickness thermal injury. Result The tissue TNF α and LBP mRNA expressions of liver, lung, intestine, and kidney were markedly increased ( P <0 05～0 01) after thermal injury. Treatment with TNF α MAb could significantly lower TNF α mRNA expression of lung, intestine and kidney, but had no effect on liver TNF α mRNA expression ( P >0 05). Similarlly, the tissue LBP mRNA expression also decreased significantly (36 0 %～72 9 %), and returned to normal in lung, intestine and kidney. In addition, biochemical parameters including GPT, TBiL, BUN, CK MB, and LDH were markedly elevated after thermal injury, and decreased significantly aftertreatment with TNF α MAb. Conclusion The increase of tissue TNF α gene expression caused by thermal injury might be associated with a marked elevation of tissue LBP mRNA expression, which could contribute to the development of multiple organ dysfunction. The early use of TNF α MAb seems to be effective in inhibiting significant LBP mRNA expression in various tissues and ameliorating multiple organ damage after major thermal injury.