期刊文献+
共找到26篇文章
< 1 2 >
每页显示 20 50 100
Enhancement of porcine in vitro embryonic development through luteolin‑mediated activation of the Nrf2/Keap1 signaling pathway
1
作者 Se-Been Jeon Pil-Soo Jeong +5 位作者 Min Ju Kim Hyo-Gu Kang Bong-Seok Song Sun-Uk Kim Seong-Keun Cho Bo-Woong Sim 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第2期600-613,共14页
Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Lut... Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development. 展开更多
关键词 LUTEOLIN Mitochondrial function nrf2/Keap1 signaling pathway Oxidative stress Porcine embryo development
下载PDF
X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway
2
作者 Ming-Wei Du Xin-Lin Zhu +8 位作者 Dong-Xing Zhang Xian-Zhen Chen Li-Hua Yang Jin-Zhou Xiao Wen-Jie Fang Xiao-Chun Xue Wei-Hua Pan Wan-Qing Liao Tao Yang 《World Journal of Diabetes》 SCIE 2024年第6期1299-1316,共18页
BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence a... BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction. 展开更多
关键词 Words:Diabetes mellitus Wound healing NF-E2-related factor-2/ho-1 signaling pathway ANDROGRAPHOLIDE
下载PDF
SIRT1/Nrf2/HO-1通路在七氟烷后处理改善失血性休克复苏小鼠空间学习与记忆障碍中的作用
3
作者 牛志伦 张丽 +3 位作者 胡溯 吴雨洁 万晓静 胡宪文 《中国药理学通报》 CAS CSCD 北大核心 2024年第3期551-556,共6页
目的探究沉默信息调节因子1(silent information regulation 1,SIRT1)/核因子E2相关因子2(nuclear transcription factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)通路在七氟烷后处理减轻脑缺血/再灌注小鼠认... 目的探究沉默信息调节因子1(silent information regulation 1,SIRT1)/核因子E2相关因子2(nuclear transcription factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)通路在七氟烷后处理减轻脑缺血/再灌注小鼠认知功能损伤中的作用。方法将♂C57BL/6J小鼠随机分为:假手术组、失血性休克复苏组、七氟烷后处理组、七氟烷后处理+SIRT1抑制剂组、七氟烷后处理+Nrf2抑制剂组,建立脑缺血/再灌注模型。水迷宫检验小鼠学习记忆能力;检测海马组织ATP、超氧化物歧化酶(superoxide dismutase,SOD)、活性氧、丙二醛含量;Western blot检测海马SIRT1、Nrf2和HO-1蛋白表达。结果再灌注后小鼠学习记忆能力降低,海马SOD、ATP含量降低,丙二醛、活性氧含量升高,SIRT1、Nrf2和HO-1蛋白表达降低;七氟烷处理后减轻了再灌注后小鼠记忆障碍和氧化应激;加用SIRT1和Nrf2抑制剂后,减弱了七氟烷对小鼠认知障碍和氧化损伤的保护作用。结论七氟烷后处理可能通过SIRT1/Nrf2/HO-1通路对失血性休克复苏引起的小鼠学习记忆障碍起到保护作用,机制与其抑制氧化应激反应相关。 展开更多
关键词 七氟烷后处理 失血性休克复苏 sirt1 nrf2 ho-1 水迷宫 氧化应激
下载PDF
Mechanism of hesperidin improving myocardial ischemia/reperfusion injury in type 2 diabetic rats through SIRT1/Nrf2/HO-1 signaling pathway
4
作者 Zhen-Wang Ma De-You Jiang +3 位作者 Bing-Cheng Hu Xing-Xing Yuan Shao-Jie Cai Jing Guo 《Journal of Hainan Medical University》 2022年第8期5-10,共6页
Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were... Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group.In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats.After then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion.He staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot;Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level,the differences were statistically significant when compared with IR group(P<0.01).In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated,the differences were statistically significant(P<0.01);Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats. 展开更多
关键词 HESPERIDIN Type 2 diabetes mellitus Ischemia/reperfusion Myocardial injury sirt1/nrf2/ho-1 signaling pathway
下载PDF
西红花苷通过调控SIRT1/Nrf2通路对心肌缺血再灌注大鼠的保护作用 被引量:7
5
作者 牛少辉 熊海燕 +1 位作者 栗媛 张丽华 《中成药》 CAS CSCD 北大核心 2023年第4期1323-1327,共5页
目的探讨西红花苷通过调控沉默信息调节因子2相关酶类1(SIRT1)/核因子E2相关因子2(Nrf2)通路对心肌缺血再灌注(I/R)大鼠心肌损伤的保护作用。方法大鼠结扎冠脉前降支40 min再灌注4 h建立I/R模型,造模成功后分为模型组、地尔硫[艹卓]组(1... 目的探讨西红花苷通过调控沉默信息调节因子2相关酶类1(SIRT1)/核因子E2相关因子2(Nrf2)通路对心肌缺血再灌注(I/R)大鼠心肌损伤的保护作用。方法大鼠结扎冠脉前降支40 min再灌注4 h建立I/R模型,造模成功后分为模型组、地尔硫[艹卓]组(10 mg/kg)和西红花苷低、中、高剂量组(20、40、80 mg/kg),另取8只正常大鼠为假手术组,连续给予相应药物15 d,ELISA法检测血清LDH、CK-MB、SOD活性和MDA水平,HE染色观察心肌组织病理改变,TUNEL染色法检测心肌细胞凋亡率,试剂盒检测心肌组织SOD活性和MDA水平,RT-qPCR和Western blot法检测心肌组织SIRT1、Nrf2、HO-1 mRNA和蛋白表达。结果与假手术组比较,模型组大鼠血清LDH和CK-MB活性、血清和心肌组织MDA水平、心肌细胞凋亡率均升高(P<0.01),血清和心肌组织SOD活性及心肌组织SIRT1、Nrf2、HO-1 mRNA和蛋白表达均降低(P<0.01),大鼠心肌纤维排列紊乱,有大片炎性浸润,多数心肌细胞破裂且核有消融现象,心肌结构模糊不清;与模型组比较,地尔硫[艹卓]组和西红花苷各剂量组血清LDH和CK-MB活性、血清和心肌组织MDA水平、心肌细胞凋亡率均降低(P<0.01),血清和心肌组织SOD活性及心肌组织SIRT1、Nrf2、HO-1 mRNA和蛋白表达均升高(P<0.01),大鼠心肌组织病理损伤均得到改善。结论西红花苷可减轻I/R大鼠心肌损伤,减少心肌细胞凋亡,其机制可能与激活SIRT1/Nrf2通路,减轻氧化应激反应有关。 展开更多
关键词 西红花苷 心肌缺血再灌注 氧化应激 sirt1 nrf2 ho-1
下载PDF
Water Extract of Rice False Smut Balls Activates Nrf2/HO-1 and Apoptosis Pathways,Causing Liver Injury
6
作者 ZHANG Guomei LI Han +4 位作者 LIU Shanshan ZHOU Xuming LU Mingyang TANG Liang SUN Lihua 《Rice science》 SCIE CSCD 2023年第5期473-485,I0025-I0028,共17页
Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice f... Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice false smut balls(RBWE) remains to be investigated.Studies have shown that RBWE may be toxic to animals,but toxicological evidence is still lacking.In this study,we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/m L,respectively,with positive correlations with dose toxicity and time toxicity.After treatment with RBWE,the number of BNL CL.2 cells decreased significantly,and the morphology of BNL CL.2 cells showed atrophy and wall detachment.RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells,increased the proportion of apoptotic cells and inhibited cell proliferation.RBWE up-regulated reactive oxygen species(ROS) levels and lowered mitochondrial membrane potentials.Additionally,Western blot and q RT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo.The contents of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE.At the same time,RBWE can lead to increases in ROS and malondialdehyde contents,decreases in contents of oxidized glutathione,glutathione and reduced glutathione,as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues,demonstrating that oxidative stress occurred in mice.Moreover,liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE.In general,RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway,which provides a reference for hepatotoxicity and its mechanism of action. 展开更多
关键词 water extract rice false smut ball ustiloxin liver injury nrf2/ho-1 pathway apoptosis pathway
下载PDF
Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway
7
作者 JIAN LI QINGQING WANG XIAOYING ZHANG 《BIOCELL》 SCIE 2023年第6期1307-1316,共10页
Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU... Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway. 展开更多
关键词 SCUTELLARIN Rheumatoid arthritis Th1/Th2 balance Keap1/nrf2/ho-1 pathway Immunosuppression
下载PDF
Effects of nuciferine on Nrf2/HO-1 signaling pathway in adipose tissue of obesity model rats
8
作者 Zhi-Xia Yang Jia-Bao Liao 《Food Therapy and Health Care》 2022年第1期1-5,共5页
Objective:This study aimed to explore the therapeutic effect of nuciferine on high-fat diet-induced obesity in rats and the influence of nuciferine on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1... Objective:This study aimed to explore the therapeutic effect of nuciferine on high-fat diet-induced obesity in rats and the influence of nuciferine on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in the adipose tissue.Methods:A total of 40 male Sprague Dawley(SD)rats were evenly divided into the normal,model,positive control,and nuciferine groups,using the random number table method.Except for the normal group,rats in the other groups were fed with high-fat diet for 12 weeks to establish the obesity model.During the model establishment,rats in the positive control group received atorvastatin calcium 2 mg/kg,rats in the nuciferine group received nuciferine 20 mg/kg,and rats in the normal and model groups received normal saline 2 mL,daily through intragastric administration for 12 consecutive weeks.After model establishment and administration,the body weight,Lee’s index,and blood lipids of rats in each group were measured,and hematoxylin and eosin(HE)staining was performed on the liver and adipose tissues to evaluate the therapeutic effect of nuciferine on obesity rat model.Additionally,the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the serum of rats in each group were determined,and the gene expressions of Nrf2 and HO-1 in the adipose tissue of rats in each group were detected through quantitative polymerase chain reaction(qPCR)to investigate the mechanism of action of nuciferine in the treatment of obesity.Results:After 12 weeks of model establishment and administration,we observed that compared with the model group,nuciferine could significantly reduce the body weight,Lee’s index,and serum triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels and increase the serum high-density lipoprotein cholesterol(HDL-C)level in obesity rat model(P<0.05 or P<0.01).HE staining revealed that nuciferine could significantly alleviate liver steatosis in obesity rat model and improve the cell morphology in epididymal adipose tissue.Moreover,nuciferine could elevate serum SOD and GSH-Px activities in obesity rat model and lower the serum MDA level(P<0.05 or P<0.01).The qPCR indicated that nuciferine could upregulate the gene expression of Nrf2 and HO-1 in the adipose tissue of obesity rat model(P<0.05 or P<0.01). 展开更多
关键词 OBESITY NUCIFERINE ANTIOXIDANT nrf2/ho-1 signaling pathway
下载PDF
橙皮苷通过SIRT1/Nrf2/HO-1信号通路改善2型糖尿病大鼠心肌缺血/再灌注损伤的机制研究 被引量:11
9
作者 马振旺 姜德友 +3 位作者 胡丙成 袁星星 蔡绍杰 郭婧 《海南医学院学报》 CAS 2022年第8期566-571,578,共7页
目的:观察橙皮苷对2型糖尿病心肌缺血/再灌注损伤的保护作用及其对SIRT1/Nrf2/HO-1信号通路的影响。方法:SD大鼠空白组、模型组、缺血再灌注组、橙皮苷组、SIRT1抑制剂组和橙皮苷+SIRT1抑制剂组,每组10只。除空白组外,余下各组大鼠均通... 目的:观察橙皮苷对2型糖尿病心肌缺血/再灌注损伤的保护作用及其对SIRT1/Nrf2/HO-1信号通路的影响。方法:SD大鼠空白组、模型组、缺血再灌注组、橙皮苷组、SIRT1抑制剂组和橙皮苷+SIRT1抑制剂组,每组10只。除空白组外,余下各组大鼠均通过高脂饮食联合链脲佐菌素腹腔注射复制2型糖尿病大鼠模型。随后采用左冠状动脉前降支结扎30 min和再灌注2 h构建心肌缺血/再灌注损伤模型。分别通过HE染色检测各组da鼠心肌组织病理形态的改变,试剂盒法检测血清LDH、CK-MB和心肌组织中SOD、GSH、MDA的水平,免疫组化和Western blot法检测心肌组织中4-HNE和SIRT1/Nrf2/HO-1信号通路中相关蛋白的表达丰度。结果:与缺血再灌注组大鼠相比,橙皮苷能够显著抑制心肌细胞坏死和炎症细胞浸润,降低LDH活性、CK-MB和MDA的水平,增加SOD活性、GSH含量和4-HNE蛋白的表达水平,差异均具有统计学意义(P<0.01)。此外,与缺血再灌注组相比,橙皮苷组SIRT1、Nrf2和HO-1蛋白的表达均显著上调,差异均具有统计学意义(P<0.01)。结论:橙皮苷通过激活SIRT1/Nrf2/HO-1信号通路抑制氧化应激,改善糖尿病心肌缺血再灌注损伤。 展开更多
关键词 橙皮苷 2型糖尿病 缺血/再灌注 心肌损伤 sirt1/nrf2/ho-1信号通路
下载PDF
螺内酯对缺氧/复氧处理的人心肌细胞HO-1/Nrf2/SIRT3信号通路及自噬的影响 被引量:3
10
作者 赵荫涛 杨海波 +3 位作者 刘源 张相钦 郑璐 徐亚威 《中国急救医学》 CAS CSCD 2021年第5期413-418,共6页
目的探讨螺内酯对缺氧/复氧(H/R)处理的人心肌细胞血红素加氧酶1(HO-1)/核因子E2相关因子2(Nrf2)/沉默信息调节因子3(SIRT3)信号通路及自噬的影响。方法体外培养人心肌细胞AC16,设置对照组(AC16细胞正常培养)、H/R组(AC16细胞经H/R处理... 目的探讨螺内酯对缺氧/复氧(H/R)处理的人心肌细胞血红素加氧酶1(HO-1)/核因子E2相关因子2(Nrf2)/沉默信息调节因子3(SIRT3)信号通路及自噬的影响。方法体外培养人心肌细胞AC16,设置对照组(AC16细胞正常培养)、H/R组(AC16细胞经H/R处理)、低剂量螺内酯组(AC16细胞经H/R处理+0.5μmol/L螺内酯)、中剂量螺内酯组(AC16细胞经H/R处理+1μmol/L螺内酯)和高剂量螺内酯组(AC16细胞经H/R处理+1.5μmol/L螺内酯)。流式细胞仪检测各组AC16细胞凋亡情况;相应试剂盒检测各组AC16细胞中超氧化物歧化酶(SOD)、丙二醛(MDA)水平;实时荧光定量PCR(qRT-PCR)法检测各组AC16细胞中HO-1、Nrf2、SIRT3 mRNA表达情况;蛋白印迹(Western blot)法检测各组AC16细胞中HO-1、Nrf2、SIRT3、微管相关蛋白1轻链3(LC3)Ⅰ、LC3Ⅱ蛋白表达情况。结果与对照组比较,H/R组AC16细胞凋亡率、MDA含量、LC3Ⅰ蛋白表达水平及LC3Ⅰ/LC3Ⅱ比值明显升高(P<0.05),SOD活性,HO-1、Nrf2、SIRT3 mRNA及蛋白表达水平和LC3Ⅱ蛋白表达水平明显降低(P<0.05);随螺内酯剂量的升高,AC16细胞凋亡率、MDA含量、LC3Ⅰ蛋白表达水平及LC3Ⅰ/LC3Ⅱ比值明显降低(P<0.05),SOD活性,HO-1、Nrf2、SIRT3 mRNA及蛋白表达水平和LC3Ⅱ蛋白表达水平明显升高(P<0.05)。结论螺内酯可能通过激活HO-1/Nrf2/SIRT3信号通路及自噬,减少经H/R处理后的人心肌AC16细胞凋亡,发挥心肌保护作用。 展开更多
关键词 螺内酯 缺氧/复氧(H/R) 心肌细胞 血红素加氧酶1/核因子E2相关因子2/沉默信息调节因子3(ho-1/nrf2/sirt3) 自噬
下载PDF
An exploration on the protective mechanism of Xuduan Zhongzi prescription against epididymis oxidative damage in oligoasthenospermia model rats based on Nrf2-NQO1/γ-GCS signaling pathway
11
作者 Zi-Li Lin Yu Wang +3 位作者 Lu Chen Liu Chen Ya-Guang Zhang Quan-Sheng Wang 《Journal of Hainan Medical University》 2022年第11期13-17,共5页
Objective:To investigate the protective mechanism of Xuduan Zhongzi prescription against epididymal oxidative damage in oligoasthenospermia model rats.Methods:Forty SD rats were randomly divided into blank group,model... Objective:To investigate the protective mechanism of Xuduan Zhongzi prescription against epididymal oxidative damage in oligoasthenospermia model rats.Methods:Forty SD rats were randomly divided into blank group,model group,Xuduan Zhongzi prescription group(10g/kg)and L-carnitine group(0.1g/kg).Except blank group,all induced oligoasmospermia.The blank group and model group were given normal saline intragastric administration,the Xuduan Zhongzi prescription group was given Xuduan Zhongzi prescription solution intragastric administration,and the L-carnitine group was given L-carnitine intragastric administration.HE staining was used to observe the epididymis structure after 8 weeks.The concentration and activity rate of epididymis sperm were measured by sperm quality.MRNA and protein expression levels of Nrf2,NQO1 andγ-GCs in epididymis were detected by RT-qPCR and immunohistochemistry.Results:①HE staining:in the blank group,the epididymis tubes were arranged tightly and regularly,the tissue structure was complete,the epithelial cells were arranged orderly,and the lumen sperm were numerous and evenly distributed.The epididymis of model group showed structural atrophy,loose arrangement,enlarged mesenchyme,increased cell debris and significantly reduced sperm cells.Compared with the model group,the lumen lesions of epididymis in Xuduan Zhongzi prescription group and L-carnitine group were significantly improved,and the amount of normal sperm in lumen was increased and the distribution was uniform.②Results of sperm quality comparison among each group:sperm density and sperm motility rate:compared with blank group,sperm density and sperm motility rate in other groups were significantly decreased(P<0.05),and sperm density and sperm motility rate in model group were significantly decreased(P<0.05);Compared with model group,the sperm density and motility rate in Xuduan Zhongzi prescription group and L-carnitine group were significantly increased(P<0.05).③RT-qPCR and immunohistochemistry:Compared with the blank group,the mRNA and protein levels of Nrf2,NQO1 andγ-GCs in epididymal rats in model group were significantly decreased(P<0.05),while the mRNA and protein levels of Nrf2,NQO1 andγ-GCs were significantly increased in L-carnitine group and Continua seed formula group(P<0.05).Conclusion:Xuduan Zhongzi prescription can reduce oxidative stress damage and improve sperm quality of oligoasthenospermia.The mechanism may related to promoting the activation of Nrf2-NQO1/γ-GCS pathway in epididymis of oligoasthenospermia rats,and up-regulate the expressions of Nrf2,NQO1 andγ-GCS proteins. 展开更多
关键词 OLIGOASTHENOSPERMIA EPIDIDYMIS Oxidative damage nrf2-NQO1/γ-GCS signaling pathways Xuduan Zhongzi prescription
下载PDF
基于SIRT1/Nrf2/HO-1通路探讨富氢水对小鼠高氧肠损伤的保护机制 被引量:2
12
作者 庄苗 李玉兰 +2 位作者 张小晓 甘露 陈苏衡 《中国急救医学》 CAS CSCD 2021年第12期1075-1080,共6页
目的研究富氢水(HRW)通过调节沉默信息调节因子1/核因子E2相关因子2/血红素加氧酶-1(SIRT1/Nrf2/HO-1)通路对小鼠高氧肠损伤发挥保护作用的机制。方法C57BL/6小鼠24只,随机分为常氧组(N组)、高氧组(O组)和富氢水组(H组)和富氢水联合SIRT... 目的研究富氢水(HRW)通过调节沉默信息调节因子1/核因子E2相关因子2/血红素加氧酶-1(SIRT1/Nrf2/HO-1)通路对小鼠高氧肠损伤发挥保护作用的机制。方法C57BL/6小鼠24只,随机分为常氧组(N组)、高氧组(O组)和富氢水组(H组)和富氢水联合SIRT1抑制剂组(HE组),每组6只。N组小鼠置于室内环境(FiO_(2)=21%)中,O组、H组和HE组小鼠置于高氧环境(FiO_(2)=85%)中,持续7 d。H组给予0.1 mL/10 g富氢水灌胃,2次/d,连续7 d;HE组在H组基础上每天腹腔注射SIRT1抑制剂EX52710 mg/kg 1次,连续7 d;N组和O组给予等体积生理盐水。每天称质量并记录小鼠体质量,7 d后安乐死小鼠并留取标本。取回肠组织制备切片并行Chiu病理评分,透射电镜观察回肠组织超微结构,检测回肠组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,Western blot检测回肠组织SIRT1、Nrf2、HO-1表达水平。结果与N组比较,O组、H组、HE组实验后小鼠体质量减轻,Chiu病理评分、MDA含量升高,SOD活性降低;与O组比较,H组实验后小鼠体质量增加,H组、HE组Chiu病理评分、MDA含量降低SOD活性升高;与H组比较,HE组实验后小鼠体质量减轻,Chiu病理评分、MDA含量升高,SOD活性降低[体质量(g):N组23.17±1.70,O组17.60±1.58,H组20.87±1.24,HE组17.20±1.27;Chiu病理评分(分):N组0.33±0.27,O组3.44±0.37,H组2.11±0.25,HE组3.06±0.23;MDA含量(nmol/mg):N组59.15±3.77,O组86.18±3.88,H组68.12±2.27,HE组76.94±5.26;SOD活性(U/mg):N组105.51±7.67,O组64.58±4.62,H组86.45±5.51,HE组72.43±4.27;均P<0.05]。与N组比较,O组SIRT1表达下调,Nrf2、HO-1表达上调,H组、HE组SIRT1、Nrf2、HO-1表达上调;与O组比较,H组SIRT1、Nrf2、HO-1表达上调,HE组SIRT1、Nrf2表达上调;与H组比较,HE组SIRT1、Nrf2、HO-1表达下调(SIRT1:N组0.17±0.01,O组0.13±0.01,H组0.66±0.04,HE组0.36±0.01;Nrf2:N组0.07±0.01,O组0.23±0.02,H组0.54±0.02,HE组0.38±0.02;HO-1:N组0.37±0.01,O组0.42±0.02,H组0.56±0.02,HE组0.44±0.02;均P<0.05)。结论富氢水预处理可通过激活SIRT1/Nrf2/HO-1信息通路,对小鼠高氧肠损伤发挥保护作用。 展开更多
关键词 高氧 肠损伤 富氢水(HRW) sirt1/nrf2/ho-1通路 氧化应激
下载PDF
Rosmarinic acid elicits neuroprotection in ischemic stroke via Nrf2 and heme oxygenase 1 signaling 被引量:10
13
作者 Hai-Ying Cui Xiang-Jian Zhang +4 位作者 Yi Yang Cong Zhang Chun-Hua Zhu Jiang-Yong Miao Rong Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第12期2119-2128,共10页
Rosmarinic acid(RA) can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in... Rosmarinic acid(RA) can elicit a neuroprotective effect against ischemic stroke, but the precise molecular mechanism remains poorly understood. In this study, an experimental ischemic stroke model was established in CD-1 mice(Beijing Vital River Laboratory Animal Technology, Beijing, China) by occluding the right middle cerebral artery for 1 hour and allowing reperfusion for 24 hours. After intraperitoneally injecting model mice with 10, 20, or 40 mg/kg RA, functional neurological deficits were evaluated using modified Longa scores. Subsequently, cerebral infarct volume was measured using TTC staining and ischemic brain tissue was examined for cell apoptosis with TUNEL staining. Superoxide dismutase activity and malondialdehyde levels were measured by spectrophometry. Expression of heme oxygenase-1(HO-1), nuclear factor erythroid 2-related factor 2(Nrf2), Bcl-2, Bax, Akt, and phospho-Ser473 Akt proteins in ischemic brain tissue was detected by western blot, while mRNA levels of Nrf2, HO-1, Bcl-2, and Bax were analyzed using real time quantitative PCR. In addition, HO-1 enzyme activity was measured spectrophotometrically. RA(20 and 40 mg/kg) greatly improved neurological function, reduced infarct volume, decreased cell apoptosis, upregulated Bcl-2 protein and mRNA expression, downregulated Bax protein and mRNA expression, increased HO-1 and Nrf2 protein and mRNA expression, increased superoxide dismutase activity, and decreased malondialdehyde levels in ischemic brain tissue of model mice. However, intraperitoneal injection of a HO-1 inhibitor(10 mg/kg zinc protoporphyrin IX) reversed the neuroprotective effects of RA on HO-1 enzyme activity and Bcl-2 and Bax protein expression. The PI3 K/Akt signaling pathway inhibitor LY294002(10 mM) inhibited Akt phosphorylation, as well as Nrf2 and HO-1 expression. Our findings suggest that RA has anti-oxidative and anti-apoptotic properties that protect against ischemic stroke by a mechanism involving upregulation of Nrf2 and HO-1 expression via the PI3 K/Akt signaling pathway. 展开更多
关键词 cerebral ischemia/reperfusion rosmarinic acid cellular apoptosis oxidative injury NEUROPROTECTION Bcl-2 Bax nrf2 heme oxygenase 1 PI3K/Akt signal pathway neural regeneration
下载PDF
Yiqi Yangyin and Huatan Quyu granule can improve skeletal muscle energy metabolism in a type 2 diabetic rat model by promoting the AMPK/SIRT/PGC-1α signalling pathway
14
作者 Wei Huang Jinna Liu +3 位作者 Jing Zhao Bangzhong Wang Biyuan Liu Ming Xie 《Journal of Traditional Chinese Medical Sciences》 2018年第2期128-138,共11页
Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the pro... Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway. 展开更多
关键词 TYPE 2 diabetes mellitus (T2DM) Yiqi Yangyin and Huatan Quyu GRANULE (YYHQ) Skeletal muscle Energy metabolism AMPK/sirt/PGC-1α signalling pathway
下载PDF
Liaoqiao aqueous extract inhibits B16 melanoma growth involving MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation
15
《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期112-112,共1页
Aim Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM) with heat-clearing and detoxicating properties. In this study, we aimed to stud... Aim Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM) with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ. 展开更多
关键词 FORSYTHIA suspensa antitumor ANTI-INFLAMMATION ANTI-OXIDATION B16 melanoma MAPKs/nrf2/ho-1pathway
下载PDF
Effect of pestle intervention in type 2 diabetic peripheral neuropathy on Keap1/Nrf2/ARE pathway and the relationship with oxidative stress
16
作者 Fang Wang Hui Yang +4 位作者 Shun-Qi Liao Yao Wang Han Wang Xi-Mei Weng Ya-Ling Huang 《Journal of Hainan Medical University》 2022年第6期24-28,共5页
Objective:To investigate the effect of pestle needle treatment on Nrf2 pathway and the relationship with oxidative stress in diabetic peripheral neuropathy.Methods:Patients with DPN who met the inclusion criteria were... Objective:To investigate the effect of pestle needle treatment on Nrf2 pathway and the relationship with oxidative stress in diabetic peripheral neuropathy.Methods:Patients with DPN who met the inclusion criteria were randomly divided into control and test groups with 30 patients in each group in a 1:1 allocation ratio.Both groups were given basic treatment,and the pestle group was treated with needle pestle therapy 5 times a week for a total of 4 weeks of intervention.Serum SOD and GSH PX levels were examined by colorimetry before and after intervention;Serum Keap1/Nrf2/ARE signaling pathway related factors expression levels were measured by ELISA;Keap1 and Nrf2 mRNA expression was determined by RT-PCR.Results:Compared with the control group,SOD and GSH-Px in the test group were significantly increased,Keap1 expression was decreased,Nrf2 expression was increased,Keap1 mRNA expression was significantly decreased,and Nrf2 mRNA expression was significantly increased.Conclusions:the pestle needle may enhance the body's antioxidant capacity by modulating the Keap1/Nrf2/ARE signaling pathway to enhance the production of its downstream antioxidant enzymes SOD and GSH Px,thereby protecting and repairing the damaged peripheral nerves in DPN patients. 展开更多
关键词 Diabetic peripheral neuropathy Pestle needle Oxidative stress Keap1/nrf2/ARE signaling pathway
下载PDF
盐酸纳美芬缺血后处理通过Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻大鼠肺缺血-再灌注损伤 被引量:1
17
作者 徐标 李鸣 +3 位作者 王继武 李文华 高锐 胡洪琳 《中华结核和呼吸杂志》 CAS CSCD 北大核心 2023年第10期993-1001,共9页
目的研究纳美芬缺血后处理通过激活Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻肺缺血-再灌注损伤的作用及其机制。方法将60只大鼠随机均分为假手术组、模型组(I/R)、纳美芬组、纳美芬+EX527组、纳美芬+ML385组、纳美芬+Fe-柠檬酸盐组共6组,每... 目的研究纳美芬缺血后处理通过激活Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻肺缺血-再灌注损伤的作用及其机制。方法将60只大鼠随机均分为假手术组、模型组(I/R)、纳美芬组、纳美芬+EX527组、纳美芬+ML385组、纳美芬+Fe-柠檬酸盐组共6组,每组10只。假手术组大鼠不行缺血再灌注处理,未予药物治疗。I/R组大鼠采用阻断左肺门法建立肺缺血-再灌注模型,未给予药物治疗。纳美芬组大鼠于肺循环再灌注前5 min予尾静脉注射纳美芬(15μg/kg)。纳美芬+EX527组、纳美芬+ML385组、纳美芬+Fe-柠檬酸盐组分别于造模前2 h腹腔注射EX527(5 mg/kg)、ML385(30 mg/kg)、Fe-柠檬酸盐(15 mg/kg),同时在肺循环再灌注前5 min时尾静脉注射纳美芬(15μg/kg)。各组大鼠于再灌注3 h末留取处死后留取左肺上叶组织,检测肺组织湿/干重比值,评估各组大鼠肺组织损伤程度,检测肺组织Fe^(2+)、MDA和TNF-α、IL-6含量、GSH活性以及Sirt1、Nrf2、HO-1、ACSL4、GPX4表达水平。结果与假手术组比较,模型组湿/干重比值、肺组织损伤评分、ACSL4表达水平、Fe^(2+)、TNF-α、IL-6和MDA含量、Sirt1、Nrf2、HO-1信使RNA及蛋白表达水平显著增高(P<0.01),GPX4表达水平及GSH活性显著下降(P<0.01)。与模型组比较,纳美芬组、纳美芬+EX527组湿/干重比值、肺组织损伤评分、ACSL4表达水平、Fe^(2+)、TNF-α、IL-6和MDA含量显著下降(P<0.01),Nrf2、HO-1信使RNA及蛋白表达水平、GPX4表达水平及GSH活性显著增高(P<0.01);其中纳美芬组Sirt1信使RNA及蛋白表达水平显著增高(P<0.01)而纳美芬+EX527组无显著变化(P>0.05)。纳美芬+ML385组湿/干重比值、肺组织损伤评分、TNF-α、IL-6含量显著下降(P<0.01),Sirt1信使RNA及蛋白表达水平显著增高(P<0.01),Nrf2、HO-1信使RNA及蛋白表达水平、ACSL4和GPX4表达水平、Fe^(2+)、MDA含量和GSH活性无显著变化(P>0.05)。纳美芬+Fe-柠檬酸盐组湿/干重比值、肺组织损伤评分、TNF-α、IL-6、MDA含量显著下降(P<0.01);Sirt1、Nrf2、HO-1信使RNA及蛋白表达水平、GSH活性显著增高(P<0.01);Fe^(2+)含量、ACSL4和GPX4表达水平无显著变化(P>0.05)。与纳美芬组比较,纳美芬+EX527组、纳美芬+ML385组、纳美芬+Fe-柠檬酸盐组湿/干重比值、肺组织损伤评分、ACSL4表达水平、Fe^(2+)、TNF-α、IL-6和MDA含量显著增高(P<0.01)、GPX4表达水平及GSH活性显著下降(P<0.01);纳美芬+EX527组Sirt1、Nrf2、HO-1信使RNA及蛋白表达水平显著下降(P<0.01);纳美芬+ML385组Nrf2、HO-1信使RNA及蛋白表达水平显著下降(P<0.01),Sirt1信使RNA及蛋白表达水平无显著变化(P>0.05);纳美芬+Fe-柠檬酸盐组Sirt1、Nrf2、HO-1信使RNA及蛋白表达水平无显著变化(P>0.05)。结论盐酸纳美芬缺血后处理可通过激活Sirt1/Nrf2/HO-1轴抑制铁死亡途径减轻肺缺血-再灌注损伤。 展开更多
关键词 盐酸纳美芬 缺血后处理 肺缺血-再灌注损伤 sirt1/nrf2/ho-1信号通路 铁死亡
原文传递
Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts 被引量:1
18
作者 WANG Teng-da XU Song-lin +3 位作者 YU Zheng-yi Nl Shao-bin ZHANG Cheng JIAO Zhi-xing 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2021年第10期760-766,共7页
Objective:To investigate the molecular mechanisms underlying the effects of arsenic trioxide(As_(2)0_(3))in combination with leflunomide on the hamster-to-rat heart xenotransplant.Methods:Transplantation of LVG hamste... Objective:To investigate the molecular mechanisms underlying the effects of arsenic trioxide(As_(2)0_(3))in combination with leflunomide on the hamster-to-rat heart xenotransplant.Methods:Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique.Four groups of recipient rats(n=6 in each)were treated with normal saline(control),As_(2)0_(3)[5 mg/(kg*day)intraperitoneally],leflunomide[5 mg/(kg*d)orally],or leflunomide[5 mg/(kg.d)+As_(2)0_(3)5 mg/(kg.d)]in combination.Donor hearts and/or rat spleens were harvested and analyzed 4 days after transplantation.Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were performed to detect the expression of the nuclear factor erythroid-derived factor 2-related factor(Nrf2)and its target gene heme oxygenase-1(HO-1),Treg cell marker fork-head Box P3(FOXP3),apoptosis-associated proteins Bcl-2,Bax,and cleaved caspase-3.Immunohistochemical staining was used to detect the levels of inflammatory natural killer cell and macrophage infiltration,intercellular cell adhesion molecule-1(ICAM-1)and complement C3.Results:Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As_(2)0_(3) plus leflunomide compared with control rats or rats treated with either drug alone(P<0.01),and this was accompanied by an increased Treg cells in the recipient rat spleen(P<0.01).In contrast,the expressions of Bax,cleaved caspase-3,ICAM-1,and complement C3,and infiltration of inflammatory cells in the xenografts were inhibited by As_(2)0_(3) plus leflunomide treatment(P<0.01).Conclusion:Combination treatment with As_(2)0_(3) and leflunomide protected hamster heart-xenografts in recipient rats. 展开更多
关键词 arsenic trioxide LEFLUNOMIDE nrf2-ARE-ho-1 signaling pathway inflammation infiltration XENOTRANSPLANTATION
原文传递
基于降低氧化应激损伤探究解毒益智方改善APP/PS1阿尔茨海默病小鼠神经毒性作用机制 被引量:3
19
作者 王田野 张鹏起 +4 位作者 朱晓婷 冯丽娜 王嘉乐 崔婷婷 黎明全 《中国老年学杂志》 CAS 北大核心 2022年第6期1440-1445,共6页
目的 观察解毒益智方(JDYZF)对APP/PS1阿尔茨海默病(AD)小鼠氧化应激水平的影响,并探究其作用机制。方法 选取4月龄C57BL/6型小鼠10只作为空白组,同月龄雄性APP/PS1小鼠40只随机分为模型组(n=10)、多奈哌齐组(n=10)、JDYZF低剂量(n=10)... 目的 观察解毒益智方(JDYZF)对APP/PS1阿尔茨海默病(AD)小鼠氧化应激水平的影响,并探究其作用机制。方法 选取4月龄C57BL/6型小鼠10只作为空白组,同月龄雄性APP/PS1小鼠40只随机分为模型组(n=10)、多奈哌齐组(n=10)、JDYZF低剂量(n=10)、JDYZF高剂量组(n=10),连续给药8 w后进行Morris水迷宫实验以观察各组小鼠逃避潜伏期、小鼠穿越平台次数和目标象限停留时间;苏木素-伊红(HE)染色观察小鼠脑组织海马CA1区的组织病理学变化;采用紫外分光光度法测定海马组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)的含量;采用免疫组化法检测SIRT1、Nrf2及HO-1蛋白表达;采用实时荧光定量-聚合酶链式反应(PCR)检测小鼠海马组织SIRT1、Nrf2、HO-1 mRNA基因表达水平。结果 JDYZF对AD小鼠空间学习及记忆能力受损具有良好改善作用;HE染色结果表明:JDYZF低剂量治疗后,对AD造成的小鼠神经元细胞毒性具有很好保护作用;JDYZF低剂量组可降低MDA含量、增加抗氧化应激SOD和GSH-Px含量,增加抗氧化蛋白SIRT1、Nrf2、HO-1的阳性细胞数,提高SIRT1、HO-1、Nrf2 mRNA表达水平,差异具有统计学意义(P<0.05)。结论 JDYZF可明显改善APP/PS1小鼠空间学习记忆能力,可能通过调节SIRT1/Nrf2/HO-1信号通路,对抗机体氧化应激水平失衡造成的损伤,治疗AD。 展开更多
关键词 解毒益智方 阿尔茨海默病 氧化应激 sirt1/nrf2/ho-1信号通路
下载PDF
Garcinia xanthochymus extract protects PC12 cells from H2O2-induced apoptosis through modulation of PI3K/AKT and NRF2/HO-1 pathways 被引量:6
20
作者 XU Jing GAN Sheng +4 位作者 LI Jun WAND De-Bing CHEN Yu HU Xin YANG Guang-Zhong 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2017年第11期825-833,共9页
The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in... The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit Et OAc fraction(fruit-EFr., 12.5–50 μmol·L^(-1)) of G. xanthochymus for 24 h prior to H_2O_2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes(superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases(MMP), and scavenged reactive oxygen species(ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3 K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3 K/AKT pathway and that it could suppress H_2O_2-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling pathways. 展开更多
关键词 GARCINIA xanthochymus Oxidative stress PC12 PI3K/AKT pathway nrf2/ho-1 signaling pathwayS
原文传递
上一页 1 2 下一页 到第
使用帮助 返回顶部