| 孙鹏,陈敏,张细六,等.虎杖苷通过调控HMGB1/TLR4/NF-κB信号通路对脓毒症急性肺损伤的保护作用[J].浙江中医药大学学报,2021,45(7):691-699. |
| 虎杖苷通过调控HMGB1/TLR4/NF-κB信号通路对脓毒症急性肺损伤的保护作用 |
| The Protective Effect of Polydatin on Sepsis-induced Acute Lung Injury in Rats by Regulating HMGB1/TLR4/NF-κB Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2021.07.002 |
| 中文关键词: 脓毒症 急性肺损伤 虎杖苷 炎症反应 SOD MDA HMGB1/TLR4/NF-κB信号通路 大鼠 |
| 英文关键词: sepsis acute lung injury polydatin inflammation SOD MDA HMGB1/TLR4/NF-κB signaling pathway rats |
| 基金项目:湖北省卫计委科研项目(WJ2015MB060) |
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| 中文摘要: |
| [目的]观察虎杖苷(polydatin，PD)对脓毒症急性肺损伤大鼠的保护作用，并探究其作用机制。[方法]将50只无特定病原体(specific pathogen free，SPF)级SD大鼠随机分为假手术组、模型组和PD高、中、低剂量组，每组10只。模型组和PD高、中、低剂量组大鼠采用盲肠结扎穿孔术制备脓毒症急性肺损伤模型，假手术组打开腹腔翻动盲肠后缝合。PD高、中、低剂量组大鼠分别予100、50、25mg·kg-1 PD灌胃，假手术组和模型组大鼠予等量0.5%羧甲基纤维素钠(carboxymethyl cellulose sodium，CMC-Na)灌胃，1次/d，连续7d。实验结束检测各组大鼠肺组织湿干重比(wet-to-dry weight ratio，W/D)、丙二醛(malondialdehyde，MDA)水平和超氧化物歧化酶(superoxide dismutase，SOD)活力；苏木精-伊红(hematoxylin-eosin，HE)染色观察肺组织病理变化；酶联免疫吸附检测(enzyme linked immunosorbent assay，ELISA)法检测血清肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白细胞介素-1β(interleukin-1β，IL-1β)、白细胞介素-6(interleukin-6，IL-6)水平；实时定量聚合酶链式反应(Real-time quantitative polymerase chain reaction，Real-time qPCR)法和Western blot法检测肺组织高迁移率族蛋白B1(high mobility group protein B1，HMGB1)、Toll样受体4(Toll like receptor 4，TLR4)和核因子-κB(nuclear factor-κB，NF-κB)p65 mRNA和蛋白表达水平。[结果]与假手术组比较，模型组TNF-α、IL-1β、IL-6、MDA水平升高，SOD活力降低，W/D值显著升高(P＜0.05)；与模型组比较，PD高、中剂量组TNF-α、IL-1β、IL-6、MDA水平降低，SOD活力升高，W/D值显著降低(P＜0.05)，而PD低剂量组TNF-α、IL-1β、IL-6、MDA水平，SOD活力及W/D值差异无统计学意义(P＞0.05)；PD中剂量组TNF-α、IL-1β、IL-6、MDA水平和W/D值高于PD高剂量组，低于PD低剂量组，SOD活力低于PD高剂量组，高于PD低剂量组(P＜0.05)。HE染色显示，模型组大鼠肺泡壁增厚水肿，有大量炎性细胞浸润；与模型组比较，PD高、中剂量可显著改善大鼠肺损伤，减轻肺泡壁增厚、水肿及炎性细胞浸润。Real-time qPCR和Western blot检测显示，与假手术组比较，模型组HMGB1、TLR4、NF-κB p65 mRNA和蛋白表达均增加(P＜0.05)；与模型组比较，PD高、中剂量组HMGB1、TLR4、NF-κB p65 mRNA和蛋白表达降低(P＜0.05)，PD低剂量组HMGB1、TLR4和NF-κB p65 mRNA和蛋白表达差异无统计学意义(P＞0.05)；与PD高剂量组比较，PD中、低剂量组HMGB1、TLR4和NF-κB p65 mRNA和蛋白表达增高，其中PD中剂量组HMGB1、TLR4和NF-κB p65 mRNA和蛋白表达低于PD低剂量组，差异有统计学意义(P＜0.05)。[结论]PD对大鼠脓毒症相关急性肺损伤具有保护作用，其作用机制可能与抑制HMGB1/TLR4/NF-κB信号通路的活化有关。 |
| 英文摘要: |
| [Objective] To observe the protective effect of polydatin(PD) on sepsis-induced acute lung injury in rats， and to explore its mechanism. [Methods] Fifty specific pathogen free(SPF) SD rats were randomly divided into sham operation group， model group， PD high-dose group， PD medium-dose group and PD low-dose group， with 10 rats in each group. Sepsis-induced acute lung injury model was established by cecal ligation and perforation in model group， PD high-dose group， PD medium-dose group and PD low-dose group. Rats in sham operation group were only opened the abdominal cavity and turned the cecum and sutured. Rats in PD high-dose group， PD medium-dose group and PD low-dose group were given 100， 50 and 25mg·kg-1 PD by gavage separately. Rats in sham operation group and model group were given 0.5% carboxymethyl cellulose sodium(CMC-Na) by gavage， once a day， for 7 consecutive days. At the end of the experiment， the wet-to-dry weight ratio(W/D) value， the level of malondialdehyde(MDA) and superoxide dismutase(SOD) activity in lung tissue of each group were detected. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of lung tissue of the rats. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α)， interleukin-1β(IL-1β) and interleukin-6(IL-6). Real-time quantitative polymerase chain reaction(Real-time qPCR) and Western blot were used to detect the expression levels of high mobility group protein B1(HMGB1)， Toll like receptor 4(TLR4) and nuclear factor-κB(NF-κB) p65 mRNA and protein in lung tissues. [Results] Compared with sham operation group， the levels of TNF-α， IL-1β， IL-6 and MDA in model group increased， SOD activity decreased， and the W/D value increased significantly(P＜0.05). Compared with model group， the levels of TNF-α， IL-1β， IL-6 and MDA in PD high-dose and medium-dose groups were decreased， SOD activity increased， and the W/D value was significantly reduced(P＜0.05); while the levels of TNF-α， IL-1β， IL-6， MDA， SOD activity and W/D values in PD low-dose group were not significantly different from those in model group(P＞0.05). Among them， the levels of TNF-α， IL-1β， IL-6， MDA and W/D values of PD medium-dose group were higher than those of PD high-dose group and lower than those of PD low-dose group， and SOD activity was lower than that of PD high-dose group， higher than PD low-dose group(P＜0.05). HE staining showed that the alveolar wall thickened and edema in model group， and there was a large number of inflammatory cell infiltration. Compared with model group， high and medium doses of PD can significantly relieve lung injury; reduce alveolar wall thickening， edema and inflammatory cells infiltration. The results of Real-time qPCR and Western blot showed that compared with sham operation group， the expressions of HMGB1， TLR4， NF-κB p65 mRNA and protein in model group increased(P＜0.05). Compared with model group， the expressions of HMGB1， TLR4， NF-κB p65 mRNA and protein in PD high-dose and medium-dose groups were significantly reduced(P＜0.05)， while the expression levels of HMGB1， TLR4， NF-κB p65 mRNA and protein in PD low-dose group were not significantly different from those in model group(P＞0.05). Compared with PD high-dose group， the expression of HMGB1， TLR4， NF-κB p65 mRNA and protein in PD medium-dose and low-dose groups increased; among them， the expression levels of HMGB1， TLR4， NF-κB p65 mRNA and protein in PD medium-dose group were lower than those of PD low-dose group， and the differences were statistically significant(P＜0.05). [Conclusion] PD has a protective effect on sepsis-induced acute lung injury in rats， and its mechanism may be related to inhibition of the activation of HMGB1/TLR4/NF-κB signaling pathway. |
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