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miRNA-130a 通过下调心力衰竭大鼠模型中 TNF-α 的表达来改善心功能。

miRNA-130a improves cardiac function by down-regulating TNF-α expression in a rat model of heart failure.

机构信息

Department of Cardiovascular Medicine, The First College of Clinical Medical Science, Three Gorges University, China; Yichang Central People's Hospital, Yichang City, Hubei Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8454-8461. doi: 10.26355/eurrev_201812_16545.

DOI:10.26355/eurrev_201812_16545
PMID:30556887
Abstract

OBJECTIVE

To investigate the effect of MicroRNA (miRNA)-130a on cardiac function and the expression of tumor necrosis factor-α (TNF-α) in rats with heart failure.

MATERIALS AND METHODS

The rat heart failure model (n = 30) were established, then divided into miRNA-130a group, phosphate-buffer saline (PBS) group, rAAV9 group, and sham group (n = 10 in each group). Four weeks after the operation, the cardiac ultrasound and hemodynamic determination were performed. Blood endothelin-1 (ET-1) content was measured by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was used to observe the morphology of myocardium. The expression levels of miRNA-130a and TNF-α were determined by quantitative Real Time-Polymerase Chain Reaction) (qRT-PCR). And the expression of TNF-α protein was determined by immunohistochemistry and Western blotting.

RESULTS

The rat heart failure model was successfully constructed. The miRNA-130a expression was decreased in rats with heart failure, and miRNA-130a transfection was successful. miRNA-130a improved left ventricular ejection fraction in the rat with heart failure. The blood ET-1 in miRNA-130a group was significantly lower than that of PBS group and rAAV9 group (p < 0.05). RT-PCR, Immunohistochemistry and Western blotting results showed that compared with the sham group, the expression of TNF-α in the model group was increased. And the expression of TNF-α in miRNA-130a group was significantly lower than that of PBS and rAAV9 group.

CONCLUSIONS

miRNA-130a could improve cardiac function of heart failure rat by down-regulating TNF-α.

摘要

目的

研究 MicroRNA(miRNA)-130a 对心力衰竭大鼠心功能及肿瘤坏死因子-α(TNF-α)表达的影响。

材料与方法

建立大鼠心力衰竭模型(n=30),随机分为 miRNA-130a 组、磷酸盐缓冲液(PBS)组、rAAV9 组和假手术组(每组 n=10)。术后 4 周,行心脏超声和血流动力学测定。酶联免疫吸附试验(ELISA)检测血液内皮素-1(ET-1)含量。苏木精-伊红(HE)染色观察心肌形态。采用实时定量聚合酶链反应(qRT-PCR)检测 miRNA-130a 和 TNF-α的表达水平。免疫组化和 Western blot 检测 TNF-α蛋白表达。

结果

成功建立大鼠心力衰竭模型。心力衰竭大鼠中 miRNA-130a 表达降低,miRNA-130a 转染成功。miRNA-130a 可改善心力衰竭大鼠左心室射血分数。miRNA-130a 组大鼠血液 ET-1 明显低于 PBS 组和 rAAV9 组(p<0.05)。RT-PCR、免疫组化和 Western blot 结果显示,与假手术组比较,模型组 TNF-α 表达增加;miRNA-130a 组 TNF-α 表达明显低于 PBS 组和 rAAV9 组。

结论

miRNA-130a 通过下调 TNF-α 改善心力衰竭大鼠心功能。

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