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Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats.
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2019-03-11 , DOI: 10.2147/jir.s194581 Dzhuliia Sh Dzhalilova 1 , Anna M Kosyreva 1 , Mikhail E Diatroptov 1 , Elena A Ponomarenko 1 , Ivan S Tsvetkov 1 , Natalia A Zolotova 1 , Vladimir A Mkhitarov 2 , Dmitry N Khochanskiy 1 , Olga V Makarova 1
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2019-03-11 , DOI: 10.2147/jir.s194581 Dzhuliia Sh Dzhalilova 1 , Anna M Kosyreva 1 , Mikhail E Diatroptov 1 , Elena A Ponomarenko 1 , Ivan S Tsvetkov 1 , Natalia A Zolotova 1 , Vladimir A Mkhitarov 2 , Dmitry N Khochanskiy 1 , Olga V Makarova 1
Affiliation
Purpose: The aim of the study was to characterize the severity of the systemic inflammatory response induced by lipopolysaccharide (LPS) in animals with different resistance levels to hypoxia.
Materials and methods: Two to three months old male Wistar rats (220–240 g) were divided according to hypoxia tolerance in a hypobaric chamber. After a month, they were injected intraperitoneally with Escherichia coli LPS at a dose of 1.5 mg/kg. After 3, 6 and 24 hours of LPS injection, we studied the levels of IL-1β, C-reactive protein (CRP) and TGF-β in the serum, the expression of Hif-1α and Nf-kb in the liver, morphological disorders in the lung and ex vivo production of IL-10 by splenic cells activated by ConA.
Results: In the early periods after the injection of LPS, increase in Nf-kb expression in the liver was observed only in the rats susceptible to hypoxia. After 6 hours of LPS injection, the number of neutrophils in the interalveolar septa of the lungs of rats susceptible to hypoxia was higher than in tolerant rats. This points to the development of more pronounced LPS-induced inflammation in the rats susceptible to hypoxia and is accompanied by increased expression of Hif-1α in the liver after 6 hours of LPS administration, serum IL-1β level after 3 hours and CRP level after 24 hours. The production of the anti-inflammatory cytokine IL-10 by the spleen was significantly decreased after 6 hours of LPS injection only in the animals tolerant to hypoxia. After 24 hours of LPS injection, a significant decrease in serum TGF-β level occurred in the rats tolerant to hypoxia in comparison with the control group, which improved the survival rates of the animals.
Conclusion: We have demonstrated the differences in the severity of the LPS-induced inflammatory response in male Wistar rats with different resistance levels to hypoxia. Rats susceptible to hypoxia are characterized by a more pronounced inflammatory response induced by LPS.
Keywords: tolerant, susceptible, hypoxia, inflammation, SIRS, lipopolysaccharide, Hif-1α, Nf-kb
中文翻译：
雄性 Wistar 大鼠全身炎症反应严重程度对缺氧抵抗力的依赖性。
目的：本研究的目的是描述脂多糖（LPS）在不同抗缺氧水平的动物中引起的全身炎症反应的严重程度。
材料与方法： 2-3 个月大的雄性 Wistar 大鼠（220-240 g）在低压室中根据缺氧耐受性进行分组。一个月后，他们以 1.5 mg/kg 的剂量腹腔注射大肠杆菌LPS。LPS注射3、6、24 h后，我们研究了血清中IL-1β、C反应蛋白（CRP）和TGF-β的水平，肝脏中Hif-1α和Nf-kb的表达，形态学肺部疾病和由 ConA 激活的脾细胞离体产生 IL-10。
结果：在注射LPS后的早期，仅在易缺氧的大鼠中观察到肝脏中Nf-kb表达的增加。LPS注射6小时后，易缺氧大鼠肺泡间隔中性粒细胞数量高于耐受大鼠。这表明在易受缺氧影响的大鼠中发生了更明显的 LPS 诱导的炎症，并伴随着Hif-1α 的表达增加LPS给药6小时后肝脏中，3小时后血清IL-1β水平和24小时后CRP水平。仅在耐受缺氧的动物中，LPS 注射 6 小时后，脾脏产生的抗炎细胞因子 IL-10 显着降低。LPS注射24 h后，耐缺氧大鼠血清TGF-β水平较对照组明显降低，提高了动物的存活率。
结论：我们已经证明了在不同抗缺氧水平的雄性 Wistar 大鼠中，LPS 诱导的炎症反应的严重程度存在差异。易受缺氧影响的大鼠的特征是由 LPS 诱导的更明显的炎症反应。
关键词：耐受、易感、缺氧、炎症、SIRS、脂多糖、Hif-1α、Nf-kb
更新日期：2019-03-11
Materials and methods: Two to three months old male Wistar rats (220–240 g) were divided according to hypoxia tolerance in a hypobaric chamber. After a month, they were injected intraperitoneally with Escherichia coli LPS at a dose of 1.5 mg/kg. After 3, 6 and 24 hours of LPS injection, we studied the levels of IL-1β, C-reactive protein (CRP) and TGF-β in the serum, the expression of Hif-1α and Nf-kb in the liver, morphological disorders in the lung and ex vivo production of IL-10 by splenic cells activated by ConA.
Results: In the early periods after the injection of LPS, increase in Nf-kb expression in the liver was observed only in the rats susceptible to hypoxia. After 6 hours of LPS injection, the number of neutrophils in the interalveolar septa of the lungs of rats susceptible to hypoxia was higher than in tolerant rats. This points to the development of more pronounced LPS-induced inflammation in the rats susceptible to hypoxia and is accompanied by increased expression of Hif-1α in the liver after 6 hours of LPS administration, serum IL-1β level after 3 hours and CRP level after 24 hours. The production of the anti-inflammatory cytokine IL-10 by the spleen was significantly decreased after 6 hours of LPS injection only in the animals tolerant to hypoxia. After 24 hours of LPS injection, a significant decrease in serum TGF-β level occurred in the rats tolerant to hypoxia in comparison with the control group, which improved the survival rates of the animals.
Conclusion: We have demonstrated the differences in the severity of the LPS-induced inflammatory response in male Wistar rats with different resistance levels to hypoxia. Rats susceptible to hypoxia are characterized by a more pronounced inflammatory response induced by LPS.
Keywords: tolerant, susceptible, hypoxia, inflammation, SIRS, lipopolysaccharide, Hif-1α, Nf-kb
中文翻译：
雄性 Wistar 大鼠全身炎症反应严重程度对缺氧抵抗力的依赖性。
目的：本研究的目的是描述脂多糖（LPS）在不同抗缺氧水平的动物中引起的全身炎症反应的严重程度。
材料与方法： 2-3 个月大的雄性 Wistar 大鼠（220-240 g）在低压室中根据缺氧耐受性进行分组。一个月后，他们以 1.5 mg/kg 的剂量腹腔注射大肠杆菌LPS。LPS注射3、6、24 h后，我们研究了血清中IL-1β、C反应蛋白（CRP）和TGF-β的水平，肝脏中Hif-1α和Nf-kb的表达，形态学肺部疾病和由 ConA 激活的脾细胞离体产生 IL-10。
结果：在注射LPS后的早期，仅在易缺氧的大鼠中观察到肝脏中Nf-kb表达的增加。LPS注射6小时后，易缺氧大鼠肺泡间隔中性粒细胞数量高于耐受大鼠。这表明在易受缺氧影响的大鼠中发生了更明显的 LPS 诱导的炎症，并伴随着Hif-1α 的表达增加LPS给药6小时后肝脏中，3小时后血清IL-1β水平和24小时后CRP水平。仅在耐受缺氧的动物中，LPS 注射 6 小时后，脾脏产生的抗炎细胞因子 IL-10 显着降低。LPS注射24 h后，耐缺氧大鼠血清TGF-β水平较对照组明显降低，提高了动物的存活率。
结论：我们已经证明了在不同抗缺氧水平的雄性 Wistar 大鼠中，LPS 诱导的炎症反应的严重程度存在差异。易受缺氧影响的大鼠的特征是由 LPS 诱导的更明显的炎症反应。
关键词：耐受、易感、缺氧、炎症、SIRS、脂多糖、Hif-1α、Nf-kb
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