| 黄约诺,叶威,郑青秀,潘锟镭,李献超,王世强.丹参酮IIA通过调控HMGB1的表达抑制TLR4/MyD88/NF-κB通路减轻大鼠脓毒症肺损伤[J].浙江中西医结合杂志,2023,33(11): |
| 丹参酮IIA通过调控HMGB1的表达抑制TLR4/MyD88/NF-κB通路减轻大鼠脓毒症肺损伤 |
| Tanshinone IIA regulates the expression of HMGB1 via TLR4/MyD88/NF-κB pathway in septic lung injury rats |
| 投稿时间：2023-05-16 修订日期：2023-07-15 |
| DOI： |
| 中文关键词: 大鼠，丹参酮IIA，脓毒症，肺损伤，TLR4/MyD88/NF-κB通路 |
| 英文关键词:Rats,Tanshinone IIA,Sepsis,Pulmonary injury,TLR4/MyD88/NF-κB pathway |
| 基金项目:浙江省温州市科技计划项目(NO:Y20211068) |
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| 中文摘要: |
| 目的 探讨丹参酮IIA对脓毒症大鼠肺损伤中高迁移率族蛋白B1（HMGB1）及Toll样受体4（TLR4）/髓样分化因子88（MyD88）/核转录因子-κB（NF-κB）通路的影响。方法 20只清洁级健康成年雄性Sprague-Dawley（SD）大鼠采用盲肠结扎穿孔法(CLP)造模，造模成功后随机分为四组，每组各5只，即模型组，低剂量治疗组、中剂量治疗组及高剂量治疗组。模型组腹腔注射0.9%氯化钠注射液，低、中、高剂量治疗组腹腔注射不同剂量的丹参酮IIA（5、10、20 mg/kg）。另取5只大鼠作为假手术组，开腹翻动肠道后关闭腹腔，腹腔注射0.9%氯化钠注射液。各组大鼠干预完成后等待24 h处死。测定各组肺湿/干重比（W/D），观察光镜下各组肺组织结构变化，实时荧光定量PCR（RT-PCR）检测肺组织Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核转录因子-κB（NF-κB）、高迁移率族蛋白B1（HMGB1 ） mRNA的表达。结果 与模型组比较，中、高剂量治疗组的肺组织W/D显著减小[(4.46±0.29)、(4.27±0.21)比(5.09±0.42)，P <0.05或P <0.01]；并且中、高剂量治疗组的肺组织TLR4、MyD88、NF-κB、HMGB1 mRNA表达下调[TLR4:(1.54±0.12)、(1.29±0.18)比(2.25±0.35);MyD88:(1.78±0.28)、(1.52±0.29)比(2.59±0.28);NF-κB:(1.35±0.09)、(1.09±0.30)比(1.87±0.29);HMGB1:(1.45±0.10)、(1.26±0.27)比(2.06±0.22)；P <0.01]，而低剂量治疗组肺组织TLR4、MyD88、HMGB1 mRNA的表达下调[TLR4:(1.85±0.20)比(2.25±0.35);MyD88:(2.14±0.26)比(2.59±0.28);HMGB1:(1.72±0.10)比(2.06±0.22)；P <0.05]，而NF-κB表达下调不明显，差异无统计学意义[(1.63±0.13)比(1.87±0.29),P >0.05]。光镜下低、中剂量治疗组大鼠肺组织较模型组大鼠肺组织损伤明显减轻，但较假手术组严重，高剂量治疗组肺组织受损最轻。结论 丹参酮IIA可以下调 HMGB1表达，抑制TLR4/MyD88/NF-κB通路，减少炎症因子释放来保护脓毒症大鼠肺组织。 |
| 英文摘要: |
| Objective To investigate the effects of tanshinone IIA on High Mobility Group protein B1 (HMGB1) and Toll-like receptor 4 (TLR4)/Myeloiddifferentiationfac- tor88 (MyD88)/Nuclear Factor-κB (NF-κB) pathway in septic rats with lung injury.Method 20 SPF grade SD rats were modeled using the cecal ligation and puncture method (CLP). After successful modeling, they were randomly divided into four groups with five rats in each group, namely the model group, low-dose treatment group, medium-dose treatment group, and high-dose treatment group.The model group was injected intraperitoneally with 0.9% sodium chloride injection, and the low-dose treatment group, medium-dose treatment group, and high-dose treatment group were injected intraperitoneally with different doses of tanshinone IIA (5, 10, and 20 mg/kg).Another 5 SPF grade SD rats were taken as a sham operation group, and the abdominal cavity was closed after opening and turning the intestines, and 0.9% sodium chloride injection was injected intraperitoneally. The rats in each group waited for 24h to be executed after the completion of the intervention.The lung wet / dry weight ratio ( W / D ) was measured. The changes of lung tissue structure in each group were observed under light microscope. The expression of TLR4, MyD88, NF-κB and HMGB1 mRNA in lung tissue was detected by RT-PCR.Results Compared with the model group, the medium-dose treatment group and high-dose treatment group of lung tissue wet / dry weight ratio decreased(4.46±0.29 and 4.27±0.21 vs. 5.09±0.42,P <0.05 or P <0.01).The expression of TLR4, MyD88, NF-κB, HMGB1mRNA were down regulated in the medium-dose treatment group and high-dose treatment group(TLR4:1.54±0.12 and 1.29±0.18 vs. 2.25±0.35, MyD88:1.78±0.28 and 1.52±0.29 vs. 2.59±0.28,NF-κB:1.35±0.09 and 1.09±0.30 vs. 1.87±0.29,HMGB1:1.45±0.10 and 1.26±0.27 vs. 2.06±0.22, P <0.01). However,the expression of TLR4, MyD88 and HMGB1 mRNA in lung tissue of low-dose treatment group was down regulated(TLR4:1.85±0.20 vs. 2.25±0.35, MyD88:2.14±0.26 vs. 2.59±0.28, HMGB1:1.72±0.10 vs. 2.06±0.22, P <0.05), but the expression of NF-κB was not significantly down regulated (1.63±0.13 vs. 1.87±0.29, P >0.05).Under the light microscope, the lung tissue injury of the low-dose treatment group and the medium-dose treatment group was significantly reduced compared with the model group, but more serious than the sham operation group. The high-dose treatment group had the lightest lung tissue damage compared with the model group, low-dose treatment group and middle-dose treatment group.Conclusion Tanshinone IIA can down-regulate the expression of HMGB1,inhibit TLR4 / MyD88 / NF-κB pathway, and reduce the release of inflammatory factors to protect the lung tissue of septic rats. |
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