Toll- like receptor 4 deficiency: Smaller infarcts, but nogain in function
Toll- like receptor 4 deficiency: Smaller infarcts, but nogain in function
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DOI：
10.1186/1472-6793-7-5
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发表时间：
2007-06-25
期刊：
影响因子：
--
通讯作者：
Baumgarten, Georg
中科院分区：
文献类型：
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作者：
Kim, Se-Chan;Ghanem, Alexander;Baumgarten, Georg
背景：已有报道Toll样受体4(TLR4)缺乏可缩小心肌缺血/再灌流(MI/R)后的梗塞范围。然而，对MI/R损伤的测量是有限的，并且不包括心功能。在慢性闭胸模型中，我们评估了TLR4缺陷小鼠(C3H/HeJ)在MI/R后心功能是否得到保护，以及心肌和全身细胞因子的表达是否与野生型(WT)不同。结果：TTC染色显示C3H/HeJ在缺血60min再灌注24小时后，心肌梗死范围(IS)明显小于WT组。尽管心肌梗死面积较小，但超声心动图显示C3H/HeJ和WT的功能没有差异。用左心室导管测得的左心室发展压在C3H/HeJ组较低(63.0+/-4.2 mm Hgvs 77.9+/-1.7 mm Hg，p<；0.05)。WT组血清细胞因子水平和心肌IL-6水平高于C3H/HeJ组(p<；0.05)。C3H/HeJ MI/R组与假手术组比较，IL-Iβ和IL-6表达增加(p<；0.05)，提示MI/R引起TLR4非依赖性细胞因子激活。结论：突变的TLR4信号通路虽然降低了心肌IS和血清细胞因子水平，但不能维持心肌功能。继发于无功能的TLR-4受体的炎症反应的改变，可能有助于在TLR-4突变小鼠中观察到梗死面积和功能之间的二分法。
Backgound: It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion (MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed compared to wild type (WT).Results: Infarct size (IS) in C3H/HeJ assessed by TTC staining after 60 min ischemia and 24h reperfusion was significantly smaller than in WT. Despite a smaller infarct size, echocardiography showed no functional difference between C3H/HeJ and WT. Left-ventricular developed pressure measured with a left-ventricular catheter was lower in C3H/HeJ (63.0 +/- 4.2 mmHg vs. 77.9 +/- 1.7 mmHg in WT, p < 0.05). Serum cytokine levels and myocardial IL-6 were higher in WT than in C3H/HeJ ( p < 0.05). C3H/HeJ MI/R showed increased myocardial IL-I beta and IL-6 expression compared to their respective shams ( p < 0.05), indicating TLR4-independent cytokine activation due to MI/R.Conclusion: These results demonstrate that, although a mutant TLR4 signaling cascade reduces myocardial IS and serum cytokine levels, it does not preserve myocardial function. The change in inflammatory response, secondary to a non-functional TLR-4 receptor, may contribute to the observed dichotomy between infarct size and function in the TLR-4 mutant mouse.