Dzhalilova D Sh, Silina M V, Kosyreva A M, Tsvetkov I S, Makarova O V
A. P. Avtsyn Research Institute of Human Morphology, B. V. Pet-rovsky National Research Centre of Surgery, Moscow, Russia.
Bull Exp Biol Med. 2023 Sep;175(5):704-710. doi: 10.1007/s10517-023-05930-y. Epub 2023 Oct 20.
Morphological and molecular biological features of LPS-induced systemic inflammatory response were assessed in old male Wistar rats with high (HR) and low (LR) resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal injection of E. coli O26:B6 LPS; the animals were sacrificed after 6 h. In histological sections, the number of neutrophils in the interalveolar septa and the area of necrosis in the liver were determined. The expression levels of Hif1a, Hif2a, Nfkb, Vegf, Il1b, Il6, Il10, and Tgfb mRNA in the liver and serum concentrations of HIF-1α and IL-1β were determined. In 4-6 h after LPS injection, 3 (43%) of 7 HR rats died, whereas no deaths were observed among LR rats. At 6 h after LPS injection, the number of neutrophils in the interalveolar septa of the lungs in LR rats was significantly higher than in HR rats, while the area of necrosis in the liver did not differ. At the same time, the mRNA expression levels of the proinflammatory cytokine genes Il1b and Il6 increased in the liver of both HR and LR rats, whereas the expression of Il10 increased only in HR rats. The expression of the Hif1a gene in the liver was higher in LR rats, but the content of HIF-1α protein in blood serum was higher in HR animals. These data should be taken into account when developing new approaches to the therapy of systemic inflammatory response in infectious and inflammatory diseases in the elderly.
在对缺氧具有高（HR）和低（LR）抗性的老年雄性Wistar大鼠中，评估了脂多糖（LPS）诱导的全身炎症反应的形态学和分子生物学特征。通过腹腔注射大肠杆菌O26:B6 LPS建立全身炎症反应模型；6小时后处死动物。在组织学切片中，测定肺泡间隔中的中性粒细胞数量和肝脏中的坏死面积。测定肝脏中Hif1a、Hif2a、Nfkb、Vegf、Il1b、Il6、Il10和Tgfb mRNA的表达水平以及血清中HIF-1α和IL-1β的浓度。LPS注射后4 - 6小时，7只HR大鼠中有3只（43%）死亡，而LR大鼠中未观察到死亡。LPS注射后6小时，LR大鼠肺脏肺泡间隔中的中性粒细胞数量显著高于HR大鼠，而肝脏中的坏死面积无差异。同时，HR和LR大鼠肝脏中促炎细胞因子基因Il1b和Il6的mRNA表达水平均升高，而Il10的表达仅在HR大鼠中升高。LR大鼠肝脏中Hif1a基因的表达较高，但HR动物血清中HIF-1α蛋白的含量较高。在为老年人感染性和炎症性疾病中的全身炎症反应开发新的治疗方法时，应考虑这些数据。
