摘要
目的:探讨川陈皮素对急性重症胰腺炎(SAP)大鼠肺损伤的影响及其机制。方法:采用逆行胰胆管注射5%牛磺胆酸钠法建立大鼠SAP模型,将造模成功的大鼠随机分为模型组、川陈皮素(75 mg/kg)组、EX527(SIRT1特异性阻断剂,5 mg/kg)组及川陈皮素+EX527组,另设假手术组,每组10只。腹腔注射相应药物进行干预,24 h/次,48 h后取材检测。ELISA法测定血清脂肪酶(LPS)、淀粉酶(AMS)及肺泡灌洗液(BALF)中IL-6、IL-1β、TNF-α水平;HE染色观察大鼠胰腺及肺组织病理学变化;试剂盒检测肺组织ROS、MDA、SOD水平;qRT-PCR和Western Blot检测肺组织中SIRT1、PGC-1α、NRF-1、TFAM mRNA及蛋白表达。结果:与假手术组比较,模型组大鼠胰腺和肺组织损伤明显,血清LPS、AMS水平及BALF中IL-6、IL-1β、TNF-α水平显著升高(P<0.05);肺组织中ROS、MDA水平显著升高,而SOD活性及SIRT1、PGC-1α、NRF-1、TFAM mRNA及蛋白表达显著降低(P<0.05)。与模型组比较,川陈皮素组大鼠胰腺和肺组织损伤改善明显,血清LPS、AMS水平及BALF中IL-6、IL-1β、TNF-α水平显著降低(P<0.05);肺组织中ROS、MDA水平显著降低,SOD活性及SIRT1、PGC-1α、NRF-1、TFAM mRNA及蛋白表达显著升高(P<0.05)。与川陈皮素组比较,EX527可显著抑制川陈皮素对SAP大鼠肺损伤的改善作用。结论:川陈皮素可改善SAP大鼠肺损伤,其作用机制可能与激活SIRT1/PGC-1α信号通路有关。
Objective:To investigate the effect and mechanism of nobiletin on lung injury in rats with severe acute pancreatitis(SAP).Methods:The SAP rat model was established by retrograde injection of 5%sodium taurocholate into pancreatic duct.The successful SAP rats were randomly divided into model group,nobiletin(75 mg/kg)group,EX527(a specific blocker of SIRT1,5 mg/kg)group,nobiletin with EX527(75 mg/kg nobiletin,5 mg/kg EX527)group,and sham operation group,with 10 rats in each group.Rats in each group were intraperitoneally injected with corresponding drugs,24 h/time.After 48 hours,the rats were sampled for detection.The levels of lipase(LPS)and amylase(AMS)in serum and IL-6,IL-1β and TNF-αin bronchoalveolar lavage fluid(BALF)were determined by ELISA.Histopathological changes of pancreas and lung were observed by HE staining.The levels of ROS,MDA and SOD in lung tissues were detected by the kit.The mRNA and proteins expressions of SIRT1,PGC-1α,NRF-1 and TFAM in lung tissues were detected by qRT-PCR and Western Blot.Results:Compared with sham operation group,pancreas and lung tissues were significantly damaged in model group rats,the levels of LPS and AMS in serum and IL-6,IL-1βand TNF-αin BALF were significantly increased(P<0.05),the levels of ROS and MDA in lung tissues were significantly increased,while SOD activity and the mRNA and proteins expressions of SIRT1,PGC-1α,NRF-1 and TFAM were significantly decreased(P<0.05).Compared with model group,pancreas and lung tissue injury was significantly improved in nobiletin group rats,the levels of LPS and AMS in serum and IL-6,IL-1β and TNF-αin BALF were significantly decreased(P<0.05),the levels of ROS and MDA in lung tissue were significantly decreased,SOD activity and the mRNA and proteins expressions of SIRT1,PGC-1α,NRF-1 and TFAM were significantly increased(P<0.05).Compared with nobiletin group,EX527 could significantly inhibit the improvement of nobiletin on lung injury in SAP rats.Conclusion:Nobiletin can improve lung injury in SAP rats,and the mechanism may be related to activating SIRT1/PGC-1αsignaling pathway.
作者
许慧
蒋峰华
张慧明
XU Hui;JIANG Feng-hua;ZHANG Hui-ming(Department of Critical Care Medicine,The Fourth Hospital of Changsha,Changsha 410006,China;Hengyang Hospital of Traditional Chinese Medicine,Hengyang 421001,China;Department of Obstetrics,The First Affiliated Hospital of Hengyang Medical School,University of South China,Hengyang 421001,China)
出处
《中药材》
CAS
北大核心
2022年第6期1458-1464,共7页
Journal of Chinese Medicinal Materials
基金
国家中医药管理局全国中医药创新骨干人才项目(国中医药人教函[2019]128号)
湖南中医药大学校级科研基金项目(2019XJJJ109)
作者简介
许慧(1981-),男,硕士,副主任医师,研究方向:重症医学,E-mail:809738542@qq.com;通讯作者:张慧明,E-mail:nyxuh123@126.com。
