基于NF-κB/NLRP3信号通路探讨生脉注射液对感染性休克大鼠急性肺损伤的影响及机制OA
Effects and Mechanisms of Shengmai Injection on Acute Lung Injury in Rats with Septic Shock Based on the NF-κB/NLRP3 Signaling Pathway
目的:基于NF-κB/NLRP3 信号通路,探究生脉注射液对感染性休克大鼠急性肺损伤的影响及机制.方法:将雄性SD大鼠随机分为对照组、模型组、阳性药物地塞米松组、生脉注射液组,每组10 只.通过静脉注射脂多糖构建感染性休克大鼠模型.检测各组大鼠血清内毒素的变化,测定各组大鼠的肺系数、肺组织湿/干重比,HE染色检测肺组织的病理学损伤,TUNEL染色检测肺组织细胞凋亡情况,Western blot检测肺组织中Bcl-2、Bax、cleaved caspase-3、p-p65 NF-κB/p65 NF-κB、NLRP3、裂解的Caspase-1(caspase-1 p20)、GSDMD蛋白的表达,ELISA 检测肺泡灌洗液中 IL-1β、IL-6、TNF-α 水平.结果:相对于对照组,模型组大鼠的血清内毒素水平升高(P<0.05),肺系数、肺组织湿/干重比升高(P<0.05),肺组织呈现显著病理学损伤,肺组织细胞的凋亡率升高(P<0.05),肺组织中Bcl-2 降低(P<0.05),Bax、cleaved caspase-3、p-p65 NF-κB/p65 NF-κB、NLRP3、caspase-1 p20、GSDMD 升高(P<0.05),肺泡灌洗液中IL-1β、IL-6、TNF-α 水平升高(P<0.05);相对于模型组,阳性药物组、生脉注射液组大鼠的血清内毒素水平降低(P<0.05),肺系数、肺组织湿/干重比降低(P<0.05),肺组织的病理学损伤减轻,肺组织细胞的凋亡率降低(P<0.05),肺组织中Bcl-2 升高(P<0.05),Bax、cleaved caspase-3、p-p65 NF-κB/p65 NF-κB、NLRP3、caspase-1 p20、GSDMD 降低(P<0.05),肺泡灌洗液中 IL-1β、IL-6、TNF-α水平降低(P<0.05).结论:生脉注射液能够通过抑制肺组织细胞的凋亡及肺部的炎症反应来减轻感染性休克大鼠的肺组织损伤,其机制可能与抑制NF-κB/NLRP3 信号通路相关.
Objective:To explore the effects and mechanisms of Shengmai injection on acute lung injury in rats with septic shock based on the NF-κB/NLRP3 signaling pathway.Methods:Male Sprague-Dawley(SD)rats were randomly divided into the control group,the model group,the positive drug dexamethasone group and the Shengmai injection group,with 10 rats in each group.A rat model of septic shock was construc-ted by intravenous injection of lipopolysaccharide.The serum endotoxin level of in rats in each group were de-tected.The lung coefficient and wet/dry weight ratio of rats in each group were measured.Hematoxylin-eosin(HE)staining was used to detect pathological damage in lung tissue.TUNEL staining was used to detect ap-optosis in lung tissues.The protein expression of Bcl-2,Bax,cleaved caspase-3,p-p65 NF-κB/p65 NF-κB,NLRP3,cleaved Caspase-1(caspase-1 p20)and GSDMD was detected by Western blot.The levels of IL-1β,IL-6,TNF-α in bronchoalveolar lavage fluid were detected by Enzyme-linked immunosorbent(ELISA).Results:Compared with the control group,the serum endotoxin levels of rats in the model group were increased(P<0.05),lung coefficient and wet/dry weight ratio of lung tissue increased(P<0.05),and lung tissue showed significant pathological damage,the apoptosis rate of lung histiocytes increased(P<0.05),the Bcl-2 in lung tissue decreased,while Bax,cleaved caspase-3,p-p65 NF-κB/p65 NF-κB,NLRP3,caspase-1 p20,GSDMD were increased(P<0.05),the levels of IL-1β,IL-6,TNF-α in bronchoalveolar lavage fluid increased(P<0.05).Compared with the model group,the serum endotoxin levels of the positive drug group and Shengmai injection group were decreased(P<0.05),lung coefficient and wet/dry weight ratio of lung tissue decreased(P<0.05),and pathological damage in lung tissue reduced,the apoptosis rate of lung histiocytes decreased(P<0.05),the Bcl-2 in lung tissue increased,while Bax,cleaved caspase-3,p-p65 NF-κB/p65 NF-κB,NLRP3,caspase-1 p20,GSDMD were decreased(P<0.05),the levels of IL-1β,IL-6,TNF-α in bronchoalveolar lavage fluid decreased(P<0.05).Conclusion:Shengmai injection can alle-viate lung tissue damage in rats with septic shock by inhibiting lung cell apoptosis and lung inflammation,the mechanism of which may be related to the inhibition of NF-κB/NLRP3 signaling pathway.
解欢琼;肖坛
云南省中医医院滇池院区急诊重症,云南 昆明 650031云南省宜良县中医医院针灸推拿科,云南 宜良 650000
急性肺损伤生脉注射液感染性休克NF-κB/NLRP3凋亡
Acute lung injuryShengmai injectionSeptic shockNF-κB/NLRP3Apopto-sis
《河北医学》 2026 (1)
33-39,7
云南省卫生健康委临床医学中心2022-2024年建设项目,(编号:202203AF150091)
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