王立明,冯 辉,牛泽群,孙江利,裴红红,潘龙飞.血红素加氧酶-1对急性重症胰腺炎相关肺损伤TLR4/NF-κB通路的影响[J].,2020,(4):661-664 |
血红素加氧酶-1对急性重症胰腺炎相关肺损伤TLR4/NF-κB通路的影响 |
Effect of HO-1 on TLR4/ NF-κB Pathway in Acute Necrotizing Pancreatitis-associated Acute Lung Injury |
投稿时间:2019-09-30 修订日期:2019-10-27 |
DOI:10.13241/j.cnki.pmb.2020.04.012 |
中文关键词: 急性重症胰腺炎 急性肺损伤 Toll样受体-4/核因子-κB信号通路 血红素加氧酶-1 |
英文关键词: Acute severe pancreatitis Acute lung injury TLR4/NF-?资B Heme oxygenase -1 |
基金项目:陕西省卫生科研项目(2016D015);陕西省社会发展科技攻关项目(2016SF-232);西安市科技计划项目(2017113SF/YX007(15)) |
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中文摘要: |
摘要 目的:探讨血红素加氧酶-1(HO-1)对急性重症胰腺炎相关肺损伤(PALI)Toll样受体-4(TLR4)/核因子-κB(NF-κB)信号传导通路的影响。方法:32只SD大鼠随机分为Sham组、PALI组、HO-1促进剂组、HO-1抑制剂组,每组8只。PALI组经胆胰管注入牛磺胆酸钠制备急性重症胰腺炎(ANP)动物模型。Sham组胆胰管内不注入牛磺胆酸钠,其余操作同PALI组。HO-1促进剂组于造模后30 min经腹腔注射牛血晶素75 μg/kg;HO-1抑制剂组于造模后30 min经腹腔注射锌-原卟啉20 μmol/kg。PALI组和Sham组均于造模后30 min经腹腔注射等量生理盐水。各组大鼠术后24 h,进行肺损伤学评分,统计肺湿/干重比值。检测大鼠术后24 h血清淀粉酶、TNF-α、IL-6、NGAL水平。检测大鼠术后24 h肺组织中TLR4、NF-κB p65蛋白表达。结果:PALI组肺损伤学评分、肺湿/干重比值、淀粉酶、TNF-α、IL-6、NGAL、TLR4、NF-κB p65明显高于Sham组;HO-1促进剂组肺损伤学评分、肺湿/干重比值、淀粉酶、TNF-α、IL-6、NGAL、TLR4、NF-κB p65明显低于PALI组;HO-1抑制剂组肺损伤学评分、肺湿/干重比值、淀粉酶、TNF-α、IL-6、NGAL、TLR4、NF-κB p65明显高于PALI组;差异均有统计学意义(P<0.05)。结论:HO-1能够通过抑制TLR4/NF-κB信号通路的激活,下调TNF-α、IL-6、NGAL等炎症因子的释放,从而发挥减轻急性重症胰腺炎相关肺损伤的作用。 |
英文摘要: |
ABSTRACT Objective: To explore the effect of Heme oxygenase -1(HO-1) on TLR4/ NF-κB pathway in acute necrotizing pancreatitis-associated acute lung injury. Methods: 32 SD rats were randomly divided into Sham group, PALI group, HO-1 promoter group and HO-1 inhibitor group, with 8 rats in each group. ANP animal model was prepared by injecting sodium taurocholate into biliopancreatic duct in PALI group. Sodium taurocholate was not injected into biliopancreatic tube in Sham group, and the other operations were the same as PALI group. The HO-1 promoter group was intraperitoneally injected with bovine hemagglutinin 75 μg/kg 30 min after modeling. The HO-1 inhibitor group was intraperitoneally injected with zinc-protoporphyrin 20 μmol/kg 30 min after modeling. The PALI group and Sham group were intraperitoneally injected with the same amount of normal saline 30 min after modeling. Lung injury scores were performed 24 h after surgery, and lung wet/dry weight ratio was calculated. Serum amylase, TNF-α, IL-6 and NGAL levels were detected 24 h after operation. The expressions of TLR4 and NF-κB p65 in the lung tissues of rats at 24 h after surgery were measured. Results: Lung injury scores, lung wet/dry weight ratio, amylase, TNF-α, IL-6, NGAL, TLR4 and NF-κB p65 were significantly higher in PALI group than Sham group. The lung injury scores, lung wet/dry weight ratio, amylase, TNF-α, IL-6, NGAL, TLR4 and NF-κB p65 were significantly lower in the HO-1 promoter group than those in the PALI group. Lung injury scores, lung wet/dry weight ratio, amylase, TNF-α, IL-6, NGAL, TLR4 and NF-κB p65 p65 were significantly higher in the HO-1 inhibitor group than in the PALI group. All the differences were statistically significant (P<0.05). Conclusion: HO-1 can reduce the release of inflammatory factors such as TNF-α, IL-6 and NGAL by inhibiting the activation of the TLR4/NF-κB signaling pathway, thereby reducing lung injury associated with acute severe pancreatitis. |
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