[1]梁 红,霍红艳.右美托咪定对盲肠结扎穿孔术诱导的脓毒症大鼠急性肺损伤保护作用及其与磷酸化JAK激酶2/酪氨酸磷酸化通路的关系[J].陕西医学杂志,2023,52(1):12-17.[doi:DOI:10.3969/j.issn.1000-7377.2023.01.003]
　LIANG Hong,HUO Hongyan.Protective effect of dexmedetomidine on CLP-induced acute lung injury in rats with sepsis and its relationship with JAK2/STAT3 pathway[J].,2023,52(1):12-17.[doi:DOI:10.3969/j.issn.1000-7377.2023.01.003]
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右美托咪定对盲肠结扎穿孔术诱导的脓毒症大鼠急性肺损伤保护作用及其与磷酸化JAK激酶2/酪氨酸磷酸化通路的关系
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年1期
页码:
12-17
栏目:
基础研究
出版日期:
2023-01-05

文章信息/Info

Title:
Protective effect of dexmedetomidine on CLP-induced acute lung injury in rats with sepsis and its relationship with JAK2/STAT3 pathway
作者:
梁 红; 霍红艳
(西安高新医院麻醉科,陕西 西安 710075)
Author(s):
LIANG Hong; HUO Hongyan
(Department of Anesthesiology,Xi'an Gaoxin Hospital,Xi'an 710075,China)
关键词:
脓毒症;  急性肺损伤;  右美托咪定;  血管通透性;  炎症反应;  JAK2/STAT3通路
Keywords:
Sepsis;  Acute lung injury;  Dexmedetomidine;  Vascular permeability;  Inflammatory response;  JAK2/STAT3 pathway
分类号:
R 655.3
DOI:
DOI:10.3969/j.issn.1000-7377.2023.01.003
文献标志码:
A
摘要:
目的:探讨右美托咪定对盲肠结扎穿孔术(CLP)诱导的脓毒症大鼠急性肺损伤保护作用及其与磷酸化JAK激酶2(p-JAK2)/酪氨酸磷酸化(p-STAT3)通路的关系。方法:30只健康成年雄性无病原体Wistar大鼠,随机分为对照组、模型组和DEX组,每组10只。通过ELISA法检测大鼠肺组织中的炎症细胞因子水平。通过组织学HE染色和TUNEL细胞染色分析大鼠肺组织损伤。通过市售检测试剂盒分析血清氧化应激水平。通过qRT-PCR检测肺组织凋亡相关基因的mRNA表达。通过蛋白印迹分析检测p-JAK2和p-STAT的蛋白表达。通过体内注射的FITC-BSA的光密度测量大鼠血管通透性。结果:模型组肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和单核细胞趋化蛋白1(MCP-1)水平较对照组升高(均P<0.05),而白细胞介素-10(IL-10)水平较对照组降低(P<0.05),DEX组TNF-α、IL-6、和MCP-1水平较模型组降低(均P<0.05),IL-10水平升高(P<0.05)。模型组HE染色和TUNEL染色评分较对照组升高(均P<0.05),DEX组HE染色和TUNEL染色评分较模型组降低(P<0.05)。CLP和假手术后24 h获得的肺切片的代表性图像:对照组结构正常,肺泡清晰。与对照组相比,模型组肺标本的初步观察表明存在明显的病理病变,包括严重的白细胞浸润、肺泡壁增厚、肺水肿和出血,经DEX预处理后,大鼠病变情况明显减轻。模型组血清总抗氧化剂(TAS)水平较对照组降低(P<0.05),DEX组血清TAS水平较模型组升高(P<0.05),模型组血清总氧化剂状态(TOS)水平和氧化应激指数(OSI)较对照组升高(均P<0.05),DEX组血清TOS水平和OSI指数较模型组降低(均P<0.05)。模型组B淋巴细胞瘤-2基因(Bcl-2)mRNA表达较对照组降低(P<0.05),BCL2-Associated X的蛋白质(Bax)和半胱氨酸蛋白酶-3(Caspase-3)mRNA表达升高(均P<0.05),DEX组Bcl-2 mRNA表达较模型组升高(P<0.05),Bax和Caspase-3mRNA表达降低(均P<0.05)。模型组p-JAK2和p-STAT3蛋白表达较对照组升高(P<0.05),DEX组p-JAK2和p-STAT3蛋白表达较模型组降低(均P<0.05)。模型组肺血管通透性和肠系膜血管通透性较对照组升高(均P<0.05),DEX组血管通透性较模型组降低(P<0.05)。与对照组相比,脓毒症大鼠的肺血管(A)和肠系膜(B)通透性显著增加(均P<0.05),与模型组相比,Dex可使肺血管和肠系膜的 FITC-BSA 的渗漏显著缓解(均P<0.05)。结论:DEX通过调控JAK2/STAT3 信号通路降低体内炎症反应,减少肺上皮细胞凋亡并改善肺血管通透性,从而可有效抑制与脓毒症相关的急性肺损伤。
Abstract:
Objective:To investigate the protective effect of dexmedetomidine(DEX)on acute lung injury in rats with sepsis induced by cecal ligation and puncture(CLP)and its relationship with JAK2/STAT3 pathway.Methods:A total of 30 healthy adult male pathogen-free Wistar rats were randomly divided into control group,model group and DEX group,10 rats in each group.The levels of inflammatory cytokines in rat lung tissue were detected by ELISA.Rat lung tissue damage was analyzed by histological HE staining and TUNEL cell staining.Serum oxidative stress levels were analyzed by commercially available assay kits.The mRNA expression of apoptosis-related proteins in lung tissue was detected by qRT-PCR.The protein expression of AK2 and STAT3 was detected by western blot.Rat vascular permeability was measured by optical density of in vivo injected FITC-BSA.Results:The levels of TNF-α,IL-6 and MCP-1 in the model group were higher than those in the control group,while the level of IL-10 was lower than that in the control group(all P<0.05).Compared with the model group,the levels of TNF-α,IL-6 and MCP-1 in the DEX group were decreased,and the level of IL-10 was increased(all P<0.05).The HE staining and TUNEL staining scores in the model group were higher than those in the control group,and the HE staining and TUNEL staining scores in the DEX group were lower than those in the model group(all P<0.05).Representative images of lung sections obtained 24 hours after CLP and sham surgery:the control group had normal structure and clear alveoli; compared with the control group,the preliminary observation of lung specimens in the model group showed that there were obvious pathological lesions,including severe leukocyte infiltration,alveolar wall thickening,pulmonary edema and hemorrhage; after pretreatment with DEX,the lesions in the rats were significantly alleviated.The serum TAS level in the model group was lower than that in the control group,while the serum TAS level in the DEX group was higher than that in the model group(all P<0.05).The serum TOS level and OSI index in the model group were higher than those in the control group,and the serum TOS level and OSI index in the DEX group were lower than those in the model group(all P<0.05).The expression of Bcl-2 mRNA in the model group was lower than that in the control group,while the mRNA expressions of Bax and Caspase-3 were increased(all P<0.05).The expression of Bcl-2 mRNA in the DEX group was higher than that in the model group,while Caspase-3 mRNA expression was decreased(all P<0.05).The protein expressions of p-JAK2 and p-STAT3 in the model group were higher than those in the control group,and the protein expressions of p-JAK2 and p-STAT3 in the DEX group were lower than those in the model group(all P<0.05).The pulmonary vascular permeability and mesenteric vascular permeability in the model group were higher than those in the control group,and the vascular permeability in the DEX group was lower than that in the model group(all P<0.05).Compared with the control group,the pulmonary vascular and mesenteric permeability of sepsis rats were significantly increased(all P<0.05).Compared with the model group,Dex significantly attenuated pulmonary vasculature and mesenteric FITC-BSA leakage(P<0.05).Conclusion:DEX can reduce the inflammatory response in vivo by regulating the JAK2/STAT3 signaling pathway,reduce the apoptosis of lung epithelial cells and improve pulmonary vascular permeability,thereby effectively inhibiting sepsis-related acute lung injury.

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备注/Memo

备注/Memo:
基金项目:西安市科技计划项目[20YXYJ0002(3)]
更新日期/Last Update: 2022-12-28