和厚朴酚减轻高甘油三酯血症急性胰腺炎大鼠模型的氧化应激:基于激活SIRT3-MnSOD2通路  

Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats

作　　者：蒙诺 杨慧莹[1] 陈金凤 覃颖颖 雷宇[1] 黄振宁[1] 唐国都[1] MENG Nuo;YANG Huiying;CHEN Jinfeng;QIN Yingying;LEI Yu;HUANG Zhenning;TANG Guodu(Department of Gastroenterology,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Endoscopy Center,Tumor Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院消化内科,广西南宁530021 [2]广西医科大学附属肿瘤医院内镜中心,广西南宁530021

出　　处：《南方医科大学学报》2023年第3期405-411,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(81970558);广西壮族自治区卫生和计划生育委员会中医药科技专项资助项目(GZLC16-33)。

摘　　要：目的探讨和厚朴酚调控Sirtuin-3(SIRT3)-MnSOD2通路对高甘油三酯血症急性胰腺炎(HTGP)大鼠氧化应激的作用。方法30只4周龄SD雄性大鼠随机分成普通饲养组和高脂饲养组,4周后普通饲养组随机设置为:对照(C)组和急性胰腺炎(AP)组;高脂饲养组随机设置为:高甘油三酯血症(HTG)对照组、HTGP组、和厚朴酚(HKL)治疗组,6只/组。AP组、HTGP组和HKL组经腹腔注射雨蛙肽建立AP模型,HKL组于造模后15 min腹腔注射HKL5 mg/kg。建立模型24 h后处置大鼠,检测大鼠血清甘油三酯(TG)、IL-6、TNF-α水平,HE染色观察胰腺组织病理学,试剂盒检测胰腺组织活性氧(ROS)、丙二醛(MDA)、还原型谷胱甘肽(GSH)水平,Western blot测定SIRT3、锰超氧化物歧化酶(MnSOD2)蛋白的表达水平,免疫组化法检测MnSOD2蛋白表达,透射电镜观察胰腺腺泡细胞及线粒体超微结构。结果与普通组比较,高脂组TG水平显著增高(P<0.05)。与各对照组比较,模型组IL-6、TNF-α、MDA水平均显著增高(P<0.05),GSH水平、SIRT3和MnSOD2蛋白表达均显著降低(P<0.05),HE染色显示有不同程度的水肿及炎细胞浸润,ROS荧光强度增强,电镜下腺泡细胞及线粒体超微结构损伤明显。与HTGP组比较,HKL组IL-6、TNF-α、MDA水平均显著降低(P<0.05),GSH水平、SIRT3和MnSOD2蛋白表达均显著增高(P<0.05),HE染色水肿及炎细胞浸润程度减轻,ROS荧光强度降低,电镜下腺泡细胞及线粒体超微结构损伤改善。结论HKL可能通过SIRT3-MnSOD2途径改善HTGP大鼠氧化应激水平并减轻胰腺病理损伤。Objective To determine how honokiol affects the sirtuin-3(SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis(HTGP).Methods Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks,after which the rats with normal feeding were randomized into control group and acute pancreatitis(AP)group(n=6),and those with high-fat feeding were divided into hypertriglyceridemia group,HTGP group,and honokiol treatment group(n=6).In AP,HTGP,and honokiol groups,AP models were established by intraperitoneal injection of cerulean;in honokiol group,the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection.Serum TG,IL-6,and TNF-αlevels were measured 24 h after the treatments,and pathological changes in the pancreas were observed with HE staining;The levels of reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione peroxidase(GSH)were measured,and SIRT3 and manganese superoxide dismutase(MnSOD2)expressions were detected using Western blotting and immunohistochemistry.Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria.Results Compared with the those with normal feeding,the rats with high-fat feeding had significantly elevated serum TG level(P<0.05).The rat models of AP showed significantly increased serum levels of IL-6,TNF-α,and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2,with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria.In rats with HTGP,honokiol treatment significantly decreased serum levels of IL-6,TNF-α,and MDA,increased GSH level and SIRT3 and MnSOD2 expressions,reduced ROS production,and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas.Conclusion Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP

关 键 词：急性胰腺炎 高甘油三酯血症 Sirtuin-3 氧化应激 

分 类 号：R285.5[医药卫生—中药学]