山姜素通过PI3K/Nrf2/HO-1通路减少炎症和氧化应激反应改善盲肠结扎和穿刺诱导的脓毒症大鼠的急性肺损伤  

Alpinetin alleviates acute lung injury in cecal ligation and punctureinduced sepsis rats by downregulating inflammation and oxidative stress via PI3K/Nrf2/HO-1 pathway

作　　者：任辉邦 张斌[1] 尹启超[3] 张玉红[1] 何五建[1] 李海珍[2] REN Huibang;ZHANG Bin;YIN Qichao;ZHANG Yuhong;HE Wujian;LI Haizhen(Emergency Intensive Care Unit,Emergency Center of Qinghai Provincial People’s Hospital,Xining 810001,China;Department of Dermatology,Emergency Center of Qinghai Provincial People’s Hospital,Xining 810001,China;Department of Hematology,Affiliated Hospital of Qinghai University,Xining 810001,China)

机构地区：[1]青海省人民医院急救中心EICU,西宁810001 [2]青海省人民医院急救中心皮肤科,西宁810001 [3]青海大学附属医院血液科,西宁810001

出　　处：《免疫学杂志》2021年第7期575-583,共9页Immunological Journal

基　　金：青海省卫生健康委员会课题(2017-wjzdx-13)。

摘　　要：目的研究山姜素对盲肠结扎和穿刺(cecal ligation and puncture,CLP)诱导的脓毒症大鼠的急性肺损伤的作用和机制。方法将大鼠随机分为6组:对照(Control)组、CLP组、山姜素(alpinetin)40、80和160 mg·kg^(-1)组、阳性药物对照组(Dex,10 mg·kg^(-1))组,每组9只大鼠。CLP诱导的脓毒症模型后,大鼠通过腹腔注射alpinetin(40、80和160 mg·kg^(-1))和地塞米松(10 mg·kg^(-1))。HE染色观察肺病理变化和评分,称重法测量肺水肿,动脉血气分析仪检测动脉血氧分压(PaO2)和动脉血CO2分压(PaCO2)水平,ELISA试剂盒检测BALF中MIP-2、TNF-α、IL-18、IL-10水平和肺组织中MPO、SOD活性及MDA、GSH水平,蛋白印迹法检测肺组织中Akt磷酸化水平及Nrf2、HO-1表达水平。结果与CLP组相比,山姜素80和160 mg·kg^(-1)组和阳性药物对照组大鼠肺的病理评分显著减少(P<0.05,P<0.01),大鼠PaCO2水平显著减少(P<0.05),PaO2水平显著增加(P<0.05,P<0.01),BALF中MIP-2、TNF-α、IL-18水平显著减少(P<0.05,P<0.01),IL-10水平显著增加(P<0.05,P<0.01),肺组织中MPO活性和MDA水平显著升高(P<0.05,P<0.01),SOD活性和GSH水平显著降(P<0.05,P<0.01),肺组织中Akt磷酸化、核Nrf-2、HO-1表达水平显著上调(P<0.05,P<0.01)。结论山姜素通过减少炎症和氧化应激反应来改善CLP诱导的脓毒症大鼠的急性肺损伤,这与激活PI3K/Nrf2/HO-1通路有关。To investigate the effect and mechanism of alpinetin in acute lung injury in cecal ligation and puncture(CLP)-induced sepsis rats,total of 54 rats were recruited and randomly divided into control group,CLP group,alpinetin 40,80 and 160 mg·kg^(-1)groups,and positive drug control group(Dex,10 mg·kg^(-1))group,with 9 rats in each group.CLP-induced sepsis model was constructed in rats,and the rats in corresponding groups were intraperitoneally injected with alpinetin(40,80 or 160 mg·kg^(-1))or dexamethasone(10 mg·kg^(-1)).Lung pathological changes and scores were observed by HE staining;pulmonary edema was measured by weighing method;arterial blood oxygen partial pressure(PaO2)and arterial blood CO2 partial pressure(PaCO2)levels were detected by an arterial blood gas analyzer.ELISA kits were used to detect the levels of MIP-2,TNF-α,IL-18 and IL-10 in BALF and the MPO,SOD activity,MDA and GSH levels in lung tissue,while Western blot was used to detect lung tissue Akt phosphorylation level and Nrf2,HO-1 expression levels.Compared with the CLP group,the pathological scores of the lungs in the rats of thealpinetin 80 and 160 mg·kg^(-1)groups and the positive drug control group were significantly reduced(P<0.05,P<0.01),Pa CO2 levels in rat arterial blood were significantly reduced(P<0.05),Pa O2 levels were significantly increased(P<0.05,P<0.01),and MIP-2,TNF-α,IL-18 levels in BALF were significantly reduced(P<0.05,P<0.01),IL-10 levels were significantly increased(P<0.05,P<0.01),MPO activity and MDA levels in lung tissue were significantlyincreased(P<0.05,P<0.01),SOD activity and GSH level were significantly decreased(P<0.05,P<0.01),Aktphosphorylation,nuclear Nrf-2 and HO-1 expression levels in lung tissue were significantly up-regulated(P<0.05,P<0.01).In conclusion,alpinetin can alleviate acute lung injury in CLP-induced sepsis rats by down-regulatinginflammation and oxidative stress,and the mechanism is related to the activation of PI3 K/Nrf2/HO-1 pathway.

关 键 词：山姜素 炎症 氧化应激 脓毒症 肺损伤 

分 类 号：R495.7[医药卫生—康复医学]