脑利钠肽持续输注对大鼠心肌梗死后心室重构的治疗作用。
Therapeutic effects of continuous infusion of brain natriuretic peptides on postmyocardial infarction ventricular remodelling in rats.
机构信息
Division of Cardiology, Shanghai Sixth Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 200233.
出版信息
Arch Cardiovasc Dis. 2011 Jan;104(1):17-28. doi: 10.1016/j.acvd.2010.09.006. Epub 2010 Dec 17.
BACKGROUND
Previous studies have shown protective effects of brain natriuretic peptide (BNP) against the postmyocardial infarction (MI) remodelling process. The transcription factor NF-κB is known to play an important role after MI.
AIMS
To investigate if NF-κB is involved in the protective effects of BNP against adverse post-MI remodelling.
METHODS
Rats were randomly assigned to five groups: sham-operation; MI by coronary ligation; MI treated with chronic BNP infusion; MI treated with enalapril; MI treated with BNP+enalapril. Rats were closely monitored for survival rate analysis. Rats from each group were sacrificed on days 3, 7 and 28 postoperation.
RESULTS
The results showed that chronic continuous BNP infusion achieved similar effects to enalapril therapy, as evidenced by improved survival rate within the 28-day observation period compared with MI group rats; this effect was closely associated with preserved cardiac geometry and performance. The treatment combination did not offer extra benefits in terms of survival rate. Both BNP and enalapril therapy produced higher heart tissue concentrations of cyclic guanosine monophosphate and lower expression levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin-1 and interleukin-6. These benefits were associated with lower phosphorylation levels of NF-κB subunits IκBα, p50 and p65. While enalapril significantly inhibited extracellular matrix remodelling via regulation of the protein expression ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinase and the activity of matrix metalloproteinase, these variables were not affected by BNP, indicating that the two therapies involve different mechanisms.
CONCLUSION
Chronic BNP infusion can provide beneficial effects against adverse post-MI remodelling.
背景
先前的研究表明脑钠肽（BNP）对心肌梗死后（MI）重塑过程具有保护作用。转录因子 NF-κB 已知在 MI 后发挥重要作用。
目的
研究 NF-κB 是否参与 BNP 对不良 MI 后重塑的保护作用。
方法
将大鼠随机分为五组：假手术组；冠状动脉结扎致 MI 组；慢性 BNP 输注治疗的 MI 组；依那普利治疗的 MI 组；BNP+依那普利治疗的 MI 组。密切监测大鼠的存活率分析。每组大鼠于术后 3、7 和 28 天处死。
结果
结果表明，与 MI 组大鼠相比，慢性连续 BNP 输注在 28 天观察期内实现了类似依那普利治疗的效果，提高了生存率；这一效果与保留心脏几何形状和功能密切相关。联合治疗在生存率方面没有提供额外的益处。BNP 和依那普利治疗均使心脏组织中环鸟苷酸单磷酸浓度升高，炎症细胞因子（包括肿瘤坏死因子-α、白细胞介素-1 和白细胞介素-6）的表达水平降低。这些益处与 NF-κB 亚基 IκBα、p50 和 p65 的磷酸化水平降低有关。依那普利通过调节基质金属蛋白酶/金属蛋白酶组织抑制剂的蛋白表达比值和基质金属蛋白酶的活性显著抑制细胞外基质重塑，而 BNP 则不影响这些变量，表明两种治疗方法涉及不同的机制。
结论
慢性 BNP 输注可对不良 MI 后重塑产生有益作用。
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