亚低温对急性肺损伤大鼠高迁移率族蛋白1表达的影响

Effects of hypothermia on the expression of high mobility group box 1 protein in rat lung with acute lung injury

目的 观察亚低温对急性肺损伤（ALI）大鼠肺组织高迁移率族蛋白1（HMGB1）及血清肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）表达的影响.方法 将24只雄性SD大鼠采用随机数字表法分为生理盐水组、ALI组和亚低温治疗组,每组8只.ALI组、亚低温治疗组分别给予内毒素（LPS）5 mg/kg尾静脉注射;亚低温治疗组同时采用体表降温法使大鼠肛温维持在（33.0±1.0）℃,持续4 h.观察12 h后各组大鼠肺组织病理,测定肺湿干质量比（W/D）、PaO2,并采用逆转录-PCR反应检测肺组织HMGB1 mRNA的表达,ELISA法测定血清TNF-α、IL-10浓度.结果 ①ALI组TNF-α浓度显著高于生理盐水组和亚低温治疗组（P〈0.01）;ALI组IL-10浓度显著高于生理盐水组（P〈0.01）,但低于亚低温治疗组（P〈0.05）.②ALI组HMGB1 mRNA的表达水平显著高于生理盐水组和亚低温治疗组（P〈0.01）.③ALI组肺组织出现充血、水肿、中性粒细胞浸润,亚低温治疗组肺部炎症较ALI组减轻.结论 亚低温可能通过抑制HMGB1 mRNA、TNF-α的表达,并上调抗炎介质IL-10的表达,从而减轻内毒素性大鼠肺损伤.

Objective To investigate modulatory effects of hypothermia （HT） on the expressions of high mobility group box 1 protein （HMGB1） and cytokines in serum, and to explore the protective mechanisms of HT in acute lung injury（ALl） induced by lipopolysaccharide（LPS）. Methods Twenty - four male Sprague - Dawley rats were randomly divided into three groups （ n = 8 each ） ： normal group, ALI group and HT treatment group. Rats in the ALI and HT treatment groups were administered with LPS （5 mg/kg） through the vein. In HT treatment group, rats were kept with rectal temperature （33.0 ± 1. 0）℃lasting 4 h. The animals were killed 12 h after injection of LPS, the lung wet/dry ratio and PaO2 were calculated, the histopathology of the lung injury was observed by light microscope, the expression of HMGB1 mRNA in the lung tissues were detected by RT- PCR, and the concentration of TNF -α and IL - 10 in serum were observed by ELISA. Results （1）TNF - α levels in normal group, ALI group and HT treatment group were （41.54±6. 84）, （85. 36±6.47）, and （ 66.57 ± 6.46） ng/L, respectively ; and IL - 10 levels were （ 25.03 ±6.67 ） , （ 52.45 ± 5.67 ） and （63.06 ± 7.86 ） ng,/L, the differences were significant between groups （ F = 67.34, 58.54, all P 〈 0. 01 ）. ②HMGB1 mRNA expression in normal group, ALl group and HT treatment group were 0. 453 ± 0. 190, 1. 963 ± 0. 431 and 1. 352 ± 0. 342, and the comparison between groups showed statistical signifieance（F =64.36, P 〈 0.01 ）. （3）Compared with normal group, infiltration of PMNs, capillary congestion and swelling were found in ALl group, treatment with HT could relieve the lung injury. Conclusion Hypothermia has a protective effect on rats with ALl induced by LPS,which maybe through downregulating of the expression of HMGB1 mRNA and TNF - α, and up - regulating of the expression of IL - 10.