益气养心饮对实验性心力衰竭大鼠TRL4通路的影响

Effect of Yiqi Yangxin Decoction on TRL4 pathways in rats with chronic heart failure

目的通过观察益气养心饮改善实验性心力衰竭大鼠心室重构、炎症状态相关指标,探讨中药对TLR4通路表达及炎性因子产生的影响和分子机制。方法选择4月龄Wistar雄性大鼠300只随机分出假手术组10只,剩下290大鼠造模筛选出30只,按心脏彩色多普勒超声测心脏射血分数(ejection fraction,EF)<60%随机区组分为模型组、中药组、缬沙坦组,每组各10只,以缬沙坦为阳性对照组,观察益气养心饮对慢性心力衰竭(chronic heart failure,CHF)大鼠toll样受体4(toll-like acceptor 4,TLR4)、核转录因子-κB(nuclear factor-κB,NF-κB)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)相关炎症因子表达的影响,并取心肌组织切片,采用HE在光镜下观察损伤程度。采用单因素方差分析对所有实验数据进行统计学处理。结果(1)与CHF模型组相比,各给药组CHF大鼠TNF-α、IL-6水平均明显下降,有统计学意义(P=0.000<0.05);(2)CHF模型组大鼠心肌TLR4、NF-κB蛋白表达明显高于假手术组(P=0.000<0.05);而各给药组TLR4、NF-κB蛋白表达较CHF模型组均明显下降(P=0.000<0.05);(3)各给药组CHF大鼠心肌组织经HE染色观察,其损伤均有不同程度的减轻。结论益气养心饮能够改善CHF大鼠的炎症状态,降低CHF大鼠血浆与心肌中TNF-α、IL-6的含量,抑制心肌组织TLR4、NF-κB炎症因子表达,可能是其抑制慢性心力衰竭进程的机制之一。

Objective We study effects of Chinese medicine on the expression of toll-like acceptor 4（ TLR4） pathway and the molecular mechanisms of inflammatory factors by observing the ventricular remodeling and inflammatory states of rats with experimental heart failure improved by Yiqi Yangxin Decoction. Methods From the 300 4-month-old male Wistar rats,10 rats were randomly assigned to the sham-operation group. 30 rats were selected from the rest of 290 rats by molding method,and then randomly assigned to the model group,the Chinese Medicine group and Valsartan group（ 10 in each group） according to the ejection fraction（ EF） 60%. With Valsartan group as the positive control,we investigated the expression of TLR4,nuclear factor-κB（ NF-κB）,tumor necrosis factor-α（ TNF-α） and interleukin-6（ IL-6） of rats with chronic heart failure（ CHF）. Myocardial damage was observed by microscope. All the data were processed by one-way ANOVA. Results（ 1） Compared with the CHF model group,the levels of TNF-α and IL- 6 in each group were decreased significantly（ P〈0. 05）.（ 2） The proteins expression of TLR4 and NF-κB in myocardium of the CHF model group was significantly higher than which in sham operation group（ P〈0. 05）. The expression of TLR4 and NF-κB proteins in each group was significantly de-creased compared with the CHF model group（ P〈0. 05）.（ 3） The damage of myocardial tissue in each group of rats with CHF,observed by HE immunohistochemical staining,was alleviated to varying degrees.Conclusion could improve the inflammation of rats with CHF,decrease the content TNF-α and IL-6 in the plasma and myocardium of rats,inhibit the expression of TLR4,NF-κB in myocardial tissue e,which might be one of the mechanisms for Yiqi Yangxin Decoction to inhibit the developing of CHF.