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目的探讨c-Jun氨基末端激酶(JNK)抑制剂SP600125对烫伤后胰岛素抵抗的作用及机制。方法24只SD大鼠以表格随机法分为假伤组、烫伤对照组和烫伤+SP600125组。将大鼠制成30%TBSAⅢ度烫伤模型(其中假伤组以常温模拟烫伤过程)。伤后第4天进行葡萄糖钳夹实验(烫伤+SP600125组在实验开始前2 h给予拮抗剂SP600125),检测肌肉组织胰岛素受体底物(IRS)1磷酸化丝氨酸307(Ser307)和酪氨酸的活性变化,并比较各组磷酸化JNK表达水平。结果(1)葡萄糖钳夹实验:假伤组、烫伤对照组和烫伤+SP600125组100 g/L葡萄糖输注率分别为(12.33±0.42)、(6.61±0.27)、(11.11±0.68)mg·kg-1·min-1,各组间比较,差异有统计学意义(P< 0.01)。(2)烫伤对照组与假伤组比较,肌肉组织IRS-1磷酸化Ser307和磷酸化JNK活性明显升高, IRS-1磷酸化酪氨酸活性明显降低(P<0.05)。烫伤+SP600125组与烫伤对照组比较,肌肉组织中IRS-1磷酸化Ser307和磷酸化JNK活性降低而IRS-1磷酸化酪氨酸活性增加。结论SP600125通过抑制JNK磷酸化而降低IRS-1磷酸化Ser307活性,可部分减轻烫伤后胰岛素抵抗发生。
Objective To investigate the effect of c-Jun N-terminal kinase (JNK) inhibitor SP600125 on insulin resistance after scald and its mechanism. Methods Twenty-four SD rats were randomly divided into four groups: sham injury group, burn control group and scald + SP600125 group. The rats were made into 30% TBSA degree scald model (in which the dummy injury group simulated the scald process at room temperature). Glucose clamp experiments were performed on the fourth day after injury (SP600125 antagonist was given to SP600125 group 2 hours before the start of the experiment), and the phosphorylation of serine 307 (Ser307) and tyrosine The activity of phosphorylated JNK in each group was compared. Results (1) Glucose clamp test: The infusion rates of 100 g / L glucose in sham injury group, burn control group and scald + SP600125 group were (12.33 ± 0.42) and (6.61 ± 0.27) , (11.11 ± 0.68) mg · kg-1 · min-1, respectively. There was a significant difference between the two groups (P <0.01). (2) The IRS-1 phosphorylated Ser307 and phosphorylated JNK activity in muscle tissue were significantly increased and the phosphorylated tyrosine activity in IRS-1 significantly decreased (P <0.05). Compared with scalded control group, scald + SP600125 group decreased IRS-1 phosphorylated Ser307 and phosphorylated JNK activity and IRS-1 phosphorylated tyrosine activity increased in muscle tissue. Conclusion SP600125 can reduce the IRS-1 phosphorylation of Ser307 by inhibiting the phosphorylation of JNK, which can partially relieve the post-scald insulin resistance.