NLRP3的过度激活与ARDS和损伤性机械通气诱导的肺损伤的关系

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Abstract Objective To investigate whether nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome involved in acute respiratory distress syndrome (ARDS) and lung injury induced by invasive mechanical ventilation. Methods Ten SD rats were divided into normal saline group (NS, n = 5) and oleic acid group (OA, n = 5) according to random number table method. NS group and OA group were given 0.1 mL /Kg of NS and OA via jugular vein, respectively. Two hours later, the ARDS model was determined to be successful by oxygenation index, lung injury score and lung wet-to-dry weight ratio (W/D). Another 40 male SD rats were divided into control group (n = 10) and OA group (n = 30). Two hours after anesthesia, according to different ventilation mode, OA group was divided into ARDS group, neap tide volume group (VT = 6 mL/kg) and injury ventilation group (VT = 20 mL/kg), with 10 rats in each group. The control group and ARDS group maintained spontaneous breathing, and the latter two groups were given mechanical ventilation. Carotid blood was collected at 2, 3, 4, 5 h and 6 h after anesthesia for blood gas analysis, W/D and lung injury score 6 h later were measured. RT-PCR and Western blot were used to detect the mRNA and protein expressions of NLRP3, caspase-1, interleukin (IL)-1β and IL-18 in lung tissues, respectively. Results W/D and lung injury scores in OA group were higher than those in NS group, and oxygenation index was lower than that in NS group (P < 0.01). The lung injury score and W/D in ARDS group were lower than those in injury-induced ventilation group, and higher than those in neap tide volume group and control group (all P ＜ 0.01). The pH and oxygenation index of ARDS group were lower than those of neap tide volume group, and higher than those of injury ventilation group (all P ＜ 0.05). Arterial partial pressure of carbon dioxide (PaCO2) in ARDS group was higher than that in injury ventilation group and lower than that in neap tidal volume group (all P ＜ 0.05). The protein and mRNA expressions of NLRP3, caspase-1, IL-1β and IL-18 in ARDS group were lower than those in injury ventilation group and higher than those in control group (all P ＜ 0.01). The mRNA expression of NLRP3, caspase-1, IL-1β and IL-18 in ARDS group and neap tidal volume group had no statistical significance (all P ＞ 0.05). Conclusion Overactivation of NLRP3 inflammasome is involved in ARDS and lung injury induced by invasive mechanical ventilation, intrusive mechanical ventilation further activates NLRP3 inflammasomes and aggravates lung injury, neap tidal ventilation prevents further activation of NLRP3 inflammasomes.

Key words： Acute respiratory distress syndrome Nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome Inflammation Mechanical ventilation

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	LIU Jun SHI Ying WANG Tingting ZUO Xiangrong

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LIU Jun SHI Ying WANG Tingting ZUO Xiangrong. Overactivation of nucleotide-binding oligomerization domain-like receptor protein 3 is involved in lung injury induced by acute respiratory distress syndrome and injurious mechanical ventilation[J]. 中国医药导报, 2021, 18(18): 17-21.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I18/17

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