Zhang Benwang, Zhang Xiao, Li Qiujie, Ma Fuguo, Sun Lixin, Wang Mingshan
Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China.
Ann Palliat Med. 2020 Sep;9(5):2474-2484. doi: 10.21037/apm-19-375. Epub 2020 Aug 6.
Mechanical ventilation is a dispensable work in clinical treatment and rescue, and always caused of ventilator-induced lung injury (VILI). Dexmedetomidine is a clinical drug to prevent lung injury, but its mechanism still unclear.
Thirty-six SD rats were randomly divided into three groups: self-breathing control group (Group C), high tidal volume (VT 20 mL/kg) group (Group H) and high VT + dexmedetomidine group (Group DEX). Serum, lung tissue, bronchoalveolar lavage fluid (BALF) were collected after rats were sacrificed by anesthetic drug of pentobarbital sodium. The pathological changes of lung tissue were observed by hematoxylin and eosin stain (HE staining), and the lung injury score and wet/dry (W/D) ratio were tested to assess lung injury. The total protein level in BALF and contents of the interleukin-1β (IL-1β), IL-18 in serum and BALF were detected by enzyme-linked immunosorbent assay (ELISA), the mRNA and protein expression level of NLR Family CARD Domain Containing 3 (NLRC3), NLR Family Pyrin Domain Containing 3 (NLRP3), Apoptosis associated speck-like protein containing a CARD domain (ASC) and caspase-1 were measured by qRT-PCR and Western Blotting respectively.
Compared with Group C, VILI mode of Group H were success established because of lung injury score and W/D value increased. when compared with Group H, which were decreased significantly in Group DEX (P<0.05), and the total protein level in BALF and the contents of IL-1β, IL-18 in serum and BALF of Group DEX were reduced markedly (P<0.05), Besides the mRNA and protein expression of NLRP3, ASC and caspase-1 in lung tissue of Group DEX were lowered dramatically (P<0.05). However, mRNA and protein expression of NLRC3 in lung tissue of Group DEX were up-regulated observably (P<0.05).
This study demonstrates that NLRC3 is involved in the VILI of rats, and dexmedetomidine can attenuate the VILI in rats by up-regulating the expression level of NLRC3.
机械通气是临床治疗和抢救中不可或缺的工作，但常导致呼吸机相关性肺损伤（VILI）。右美托咪定是一种预防肺损伤的临床药物，但其机制仍不清楚。
将36只SD大鼠随机分为三组：自主呼吸对照组（C组）、高潮气量（VT 20 mL/kg）组（H组）和高潮气量+右美托咪定组（DEX组）。用戊巴比妥钠麻醉药物处死大鼠后，收集血清、肺组织、支气管肺泡灌洗液（BALF）。通过苏木精-伊红染色（HE染色）观察肺组织的病理变化，并检测肺损伤评分和湿/干（W/D）比值以评估肺损伤。采用酶联免疫吸附测定（ELISA）检测BALF中的总蛋白水平以及血清和BALF中白细胞介素-1β（IL-1β）、IL-18的含量，分别用qRT-PCR和蛋白质免疫印迹法检测含CARD结构域的NLR家族成员3（NLRC3）、含pyrin结构域的NLR家族成员3（NLRP3）、含CARD结构域的凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1的mRNA和蛋白表达水平。
与C组相比，H组因肺损伤评分和W/D值升高成功建立了VILI模型。与H组相比，DEX组上述指标显著降低（P<0.05），DEX组BALF中的总蛋白水平以及血清和BALF中IL-1β、IL-18的含量明显降低（P<0.05）。此外，DEX组肺组织中NLRP3、ASC和半胱天冬酶-1的mRNA和蛋白表达显著降低（P<0.05）。然而，DEX组肺组织中NLRC3的mRNA和蛋白表达明显上调（P<0.05）。
本研究表明NLRC3参与大鼠的VILI，右美托咪定可通过上调NLRC3的表达水平减轻大鼠的VILI。
