ZHANG Hong-nan, CHEN Zhen-hui, FAN Hong-ying, ZHU Jia-wei, GUO Jin-qiang, QING Min, WANG Zhi, MENG Xiao-jing. Effects of NLRP3 inflammasome on heat stress-induced damage in mice[J]. Journal of Environmental and Occupational Medicine, 2020, 37(5): 453-460. DOI: 10.13213/j.cnki.jeom.2020.19899
Citation: ZHANG Hong-nan, CHEN Zhen-hui, FAN Hong-ying, ZHU Jia-wei, GUO Jin-qiang, QING Min, WANG Zhi, MENG Xiao-jing. Effects of NLRP3 inflammasome on heat stress-induced damage in mice[J]. Journal of Environmental and Occupational Medicine, 2020, 37(5): 453-460. DOI: 10.13213/j.cnki.jeom.2020.19899

Effects of NLRP3 inflammasome on heat stress-induced damage in mice

  • Background Heat stress (HS)-caused systemic inflammation response can lead to injuries to vital organs and even death in patients. NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) plays an important role in mediating aseptic inflammation caused by tissue injury, but its role in HS-induced damage is not clear.
    Objective This experiment explores the role of NLRP3 inflammasome in systemic inflammatory response and multiple organ damage in mice after HS.
    Methods This experiment included three groups:control group (wild type C56BL/6 male mice without HS), HS group (wild type C57BL/6 male mice with HS), and Nlrp3-/-HS group (NLRP3 knockout C57BL/6 male mice with HS), with eight mice in each group. HS was induced by exposure to an ambient temperature of (41.0±0.5)℃ with relative humidity of (65±5)%. Anal temperature and general mental and physical conditions were recorded every 15-20min. When the anal temperature of the mice in the HS group rose above 42.0℃, the HS group and the Nlrp3-/-HS group were removed to room temperature and then anesthetized and dissected after 4 h. Selected organs of the mice, such as liver, kidney, spleen, brain, and intestine, were stained with HE for histopathological examination. Levels of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 were measured with ELISA kit; level of endotoxin was detected with endotoxin kit; expression levels of intestinal Occludin and zonula occludens-1 (ZO-1), as well as NLRP3, caspase-1, and IL-1β in brain, liver, and intestine tissues were analyzed by Western blotting.
    Results After the heat exposure for 90min, the HS group showed higher anal temperature(42.1±0.2)℃ than the control group(36.6±0.2)℃, and the Nlrp3-/-HS group showed lower anal temperature(40.1±0.7)℃ and less body weight loss(1.3±0.2) g than the HS group (P < 0.05). The pathological results after HE staining showed different degrees of injury to liver, kidney, spleen, brain, and intestine in the HS group, while only mild histopathological changes in the Nlrp3-/-HS group. The levels of serum TNF-α, IL-1β, and endotoxin were higher and the expression levels of intestinal Occludin and ZO-1 were lower in the HS group than those in the control group, and the level of IL-1β was lower and the expression levels of intestinal Occludin and ZO-1 were higher in the Nlrp3-/-HS group than those in the HS group (P < 0.05). The expression levels of NLRP3, caspase-1, and IL-1β in brain, liver, and intestine tissues of mice in the HS group were higher than those in the control group (P < 0.05), while the levels in the Nlrp3-/-HS group were lower than those in the HS group (P < 0.05).
    Conclusion The activation of NLRP3 inflammasome plays a key role in systemic inflammatory response and multiple organ function damage during acute HS exposure.
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