参附黄制剂联合亚低温对脓毒症大鼠下丘脑AMPK-POMC相关靶点的影响  

Effects of Shenfuhuang Preparation combined with subhypothermia on AMPK-POMC-related targets in the hypothalamic brain of septic rats

作　　者：陈剑明[1] 彭美哲 陈奕杉 连博 赵春铭 陈腾飞[1] 何莎莎[4] 刘五江 徐霄龙[4] 杨欣怡 刘清泉[1] CHEN Jian-ming;PENG Mei-zhe;CHEN Yi-shan;LIAN Bo;ZHAO Chun-ming;CHEN Teng-fei;HE Sha-sha;LIU Wu-jiang;XU Xiao-long;YANG Xin-yi;LIU Qing-quan(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;Yanqing Hospital,Beijing Traditional Chinese Medicine Hospital,Beijing 102100,China;Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Institute of Traditional Chinese Medicine,Beijing 100010,China;The 81st Group Army Hospital of the Chinese People’s Liberation Army,Zhangjiakou 075000,China)

机构地区：[1]首都医科大学附属北京中医医院,北京100010 [2]北京中医医院延庆医院,北京102100 [3]北京中医药大学,北京100029 [4]北京市中医研究所,北京100010 [5]中国人民解放军陆军第81集团军医院,张家口075000

出　　处：《中华中医药杂志》2022年第5期2475-2480,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81673934,No.81973608,No.62041701,No.82174157);北京市自然科学基金项目(No.7192083);中国博士后科学基金资助项目(No.2019M650774);北京市属医院科研培育计划项目(No.PZ2019009,No.PZ2022014);首都医科大学校级自然项目(No.PYZ19170)。

摘　　要：目的:探讨参附黄制剂联合亚低温治疗对脓毒症大鼠下丘脑AMPK、POMC分泌的影响。方法:50只雄性SD大鼠随机平均分为正常组、模型组、参附黄组、亚低温组、联合组,每组10只。除正常组外,其余腹腔注射脂多糖的方式(5 mg/kg)制作脓毒症模型。对参附黄组、联合组在造模前0.5 h分别以参附黄制剂(20 mg/kg)灌胃,总体积为1 mL,每日1次,疗程为4 d。亚低温组、联合组用异氟醚麻醉下即刻给予亚低温治疗3 h,疗程2 d。记录大鼠每日存活率、食量。实验结束后取大鼠静脉血和下丘脑、骨骼肌组织。ELISA检测外周血血糖、胰岛素、瘦素、皮质醇。Western blot检测下丘脑相关蛋白水平。结果:与模型组比较,联合组存活率较高,进食量显著增加(P<0.01);显著降低血清血糖、胰岛素、瘦素、皮质醇水平(P<0.01,P<0.05);显著降低自噬调节蛋白LC3Ⅱ/LC3Ⅰ水平(P<0.05),显著提高p-ULK1/ULK1和p-AMPK/AMPK水平(P<0.01);显著抑制炎症因子IL-1β、TNF-α的表达(P<0.01)。结论:参附黄制剂联合亚低温干预可以提高脓毒症大鼠存活率、抑制神经肽POMC分泌、提升下丘脑AMPK磷酸化-自噬水平。Objective:To investigate the effects of Shenfuhuang Preparation combined with subhypothermia on AMPK,POMC secretion of hypothalamus in septic rats.Methods:Fifty male SD rats were randomly divided into normal group,sepsis group,Shenfuhuang group,sub hypothermia group and joint group,with 10 rats in each group.Except for the normal group,the sepsis model was made by injection of lipopolysaccharide(5 mg/kg)in the cavity.The Shenfuhuang group and joint group were irrigation total volume of Shenfuhuang(20 mg/kg)1 mL,once a day,and the course of treatment was 4 d.The subhypothermia group and joint group were given sublow temperature treatment for 3 h immediately after anesthesia with isoflurane,and the course of treatment was 2 d.To observe the survival rate of rats and food intake for each rat in each group daily.The venous blood,hypothalamic and skeletal muscle tissue were collected after the experiment.The levels of peripheral blood glucose,insulin,leptin and cortisol were detected by ELISA.The hypothalamic-related protein levels were detected by Western blot.Results:Compared with the model group,the joint group improved survival and food intake(P<0.01);and significantly reduced serum glucose,insulin,leptin and cortisol(P<0.01,P<0.05);significant decreased the autophagy regulatory protein levels of LC3Ⅱ/LC3Ⅰ(P<0.05),and significantly increased the levels of p-ULK1/ULK1 and p-AMPK/AMPK(P<0.01);and significantly suppressed the expression of the inflammatory factors of IL-1 and TNF-α(P<0.01).Conclusion:Shenfuhuang combined with mild hypothermia intervention could improve survival rate,inbit neuropeptide POMC secretion and elevate AMPK-phosphate-autophagic levels in septic rats.

关 键 词：脓毒症 参附黄制剂 亚低温疗法 POMC AMPK 存活率 代谢 保护作用 

分 类 号：R285.5[医药卫生—中药学]