Meng N, Yang H, Chen J, Qin Y, Lei Y, Huang Z, Tang G
Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Endoscopy Center, Tumor Hospital of Guangxi Medical University, Nanning 530021, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):405-411. doi: 10.12122/j.issn.1673-4254.2023.03.10.
To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP).
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 (=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (=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- levels 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.
Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level ( < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-, 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-, 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.
Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.
确定厚朴酚如何影响高甘油三酯血症诱导的急性胰腺炎（HTGP）大鼠的沉默信息调节因子3（SIRT3）-锰超氧化物歧化酶2（MnSOD2）通路及氧化应激。
将30只4周龄雄性SD大鼠随机分为两组，分别进行正常喂养和高脂喂养4周，之后将正常喂养的大鼠随机分为对照组和急性胰腺炎（AP）组（每组6只），高脂喂养的大鼠分为高甘油三酯血症组、HTGP组和厚朴酚治疗组（每组6只）。在AP组、HTGP组和厚朴酚组中，通过腹腔注射雨蛙肽建立AP模型；在厚朴酚组中，大鼠在注射雨蛙肽15分钟后腹腔注射5mg/kg厚朴酚。治疗24小时后测定血清甘油三酯（TG）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平，并用苏木精-伊红（HE）染色观察胰腺病理变化；测定活性氧（ROS）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH）水平，采用蛋白质免疫印迹法和免疫组织化学法检测SIRT3和锰超氧化物歧化酶（MnSOD2）表达。采用透射电子显微镜观察胰腺腺泡细胞和线粒体的超微结构。
与正常喂养的大鼠相比，高脂喂养的大鼠血清TG水平显著升高（P<0.05）。AP大鼠模型血清IL-6、TNF-α和MDA水平显著升高，GSH水平以及SIRT3和MnSOD2表达降低，胰腺出现明显水肿和炎性细胞浸润，ROS荧光强度增强，腺泡细胞和线粒体超微结构受损。在HTGP大鼠中，厚朴酚治疗显著降低血清IL-6、TNF-α和MDA水平，提高GSH水平以及SIRT3和MnSOD2表达，减少ROS产生，减轻胰腺腺泡细胞和线粒体超微结构损伤。
厚朴酚可能通过激活SIRT3-MnSOD2通路减轻HTGP大鼠的氧化应激并缓解胰腺损伤。
