摘要
目的研究升降散调控TLR-4/NF-κB信号通路对LPS诱导脓毒症大鼠心肌损伤的影响。方法采用腹腔注射LPS法构建急性脓毒血症大鼠模型,大鼠随机分为正常组(n=6),脓毒症模型组(n=6),中药组(n=6),抑制剂组(n=6),除正常组外,各组均腹腔注射注射脂多糖,miR-146a抑制剂组心肌内注射miR-146a抑制剂(0.2μl/g),中药组升降散灌胃。48 h后采集大鼠心肌组织,观察心肌组织切片病理改变,测定白介素-1(IL-1)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)等因子的水平,及miRNA-146a、NF-κB mRNA、TNF-αmRNA、IL-6 mRNA、IL-1βmRNA活性水平。结果与正常组相比,各组IL-1、IL-6、TLR4及NF-κB蛋白水平升高(P<0.05),模型组及抑制组TNF-α高于对照组(P<0.05);模型组miR-146a、NF-κB、TNF-α、IL-6及IL-1基因表达增高(P<0.01),中药组miR-146a及NF-κB表达增高(P<0.05);抑制剂组NF-κB、TNF-α、IL-6及IL-1表达增高(P<0.01)。与模型组相比,中药组、TNF-α、TLR4及NF-κB蛋白水平降低(P<0.05),中药组miR-146a表达增高,而NF-κB、TNF-α、IL-1及IL-6基因表达降低(P<0.05);抑制剂组IL-6、TNF-α、TLR4及NF-κB活性升高(P<0.01),抑制剂组miR-146a表达降低(P<0.01),NF-κB、TNF-α、IL-6及IL-1表达增高。与抑制剂组相比,中药组IL-1、IL-6、TNF-α、TLR4及NF-κB蛋白水平降低(P<0.01),miR-146a基因表达增高,而NF-κB、TNF-α、IL-6及IL-1表达降低(P<0.01)。结论升降散能减轻脓毒症大鼠心肌损害,其机制可能与其促进miRNA-146a表达,负反馈调节TLR-4/NF-κB信号通路,减轻抑制炎症反应有关。
Objective To investigate the effects of Shengjiang Powder on lipopolysaccharide( LPS) induced myocardial injury in septic rats via TLR-4/NF-κB signaling pathway. Methods The rat model of acute disease was established by intraperitoneal injection of LPS. The rats were randomly divided into the normal group( n = 6),sepsis model group( n = 6),Chinese medicine group( n = 6) and inhibitor group( n = 6). Except the normal group,rats in the other groups were intraperitoneally injected with lipopolysaccharide. The rats in the inhibitor group were injected with miR-146 a inhibitor( 0. 2 μl/g) by intramyocardial administration,and the rats in the Chinese medicine group were treated with Shengjiang Powder by intragastric administration. After 48 hours,the myocardial tissue was collected and homogenized,the pathological changes of myocardial tissue sections were observed. The levels of interleukin( IL)-1,IL-6,tumor necrosis factor-α( TNF-α),and the mRNA activity levels of miRNA-146 a,NF-κB,TNF-α,IL-6 and IL-1β were detected. Results Compared with the normal group,the levels of IL-1,IL-6,TLR4 and NF-κB were increased in the other groups( P<0.05). The TNF-α level in the model group and inhibitor group was higher than that in the normal group( P<0.05). The gene expressions of miR-146 a,NF-κB,TNF-α,IL-6 and IL-1 in the model group were increased( P<0.01). The expressions of miR-146 a and NF-κB in the Chinese medicine group were increased( P<0.05). The expressions of NF-κB,TNF-α,IL-6 and IL-1 in the inhibitor group were increased( P<0.01). Compared with the model group,the protein levels of TNF-α,TLR4 and NF-κB were decreased in the Chinese medicine group( P<0.05),and the expression of miR-146 a was increased,while the gene expressions of NF-κB,TNF-α,IL-1 and IL-6 were decreased( P<0.05). Compared with the model group,the activities of IL-6,TNF-α,TLR4 and NF-κB in the inhibitor group were increased( P<0.01),and the expression of miR-146 a was decreased( P<0.01),while the expressions of NF-κB,TNF-α,IL-6 and I
出处
《上海中医药杂志》
2018年第10期82-86,共5页
Shanghai Journal of Traditional Chinese Medicine
基金
上海市虹口区卫计委资助项目(虹卫1502-04)
