赵瑄,甘婷,王雨虹,巨佳曦,朱贵明
ZHAO Xuan,GAN Ting,WANG Yuhong,JU Jiaxi,ZHU Guiming

• 1:贵州医科大学生物与工程学院
• 2:贵州医科大学健康医药现代产业学院

摘要(Abstract)：

目的 探讨多不饱和脂肪酸(PUFAs)对Δ15脂肪酸去饱和酶(Δ15 Des)转基因小鼠前列腺素E_2(PGE_2)水平的影响。方法 取C57BL/6野生型(WT)雄性小鼠和Δ15 Des转基因雄性小鼠作为对照组(n=5,WT组)和实验组(n=5,TG组),6%花生四烯酸(ARA)饲养8周，每周记录小鼠体质量变化；8周后麻醉处死2组小鼠，冰上分离小鼠肝脏、睾丸及肌肉组织，采用气相色谱(GC)检测2组小鼠各组织中脂肪酸(FAs)的组成及水平，采用酶联免疫吸附(ELISA)和实时荧光定量PCR(RT-qPCR)测定2组小鼠各组织中PGE_2的水平及前列腺素E合酶1(PTGES1)、前列腺素E合酶2(PTGES2)信使RNA(mRNA)的相对表达。结果 第1～8周，2组小鼠体质量均在增长，2组间比较、差异无统计学意义(P>0.05);WT组小鼠各组织中PUFAs主要是欧米伽-6 PUFAs(n-6 PUFAs);与WT组相比，TG组小鼠各组织中ARA水平降低、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)水平升高(P<0.05或P<0.01),睾丸组织中亚油酸(LA)水平升高、二十二碳四烯酸(DTA)水平降低(P<0.05);TG组小鼠睾丸、肌肉组织中PGE_2水平低于WT组(P<0.05或P<0.01);TG组小鼠肝脏、睾丸组织中PTGES1、PTGES2 mRNA表达低于WT组(P<0.05或P<0.01)。结论 PUFAs可减少Δ15 Des转基因小鼠ARA的合成，降低与PGE_2相关的合成酶表达，从而调节体内PGE_2的水平。
Objective To investigate the effect of polyunsaturated fatty acids(PUFAs) on prostaglandin E_2(PGE_2) content in transgenic mice with Δ15 fatty acid desaturase(Δ15 Des). Methods C57BL/6 wild-type(WT) male mice and Δ15 Des transgenic male mice were chosen as control group(n=5,WT group) and experimental group(n=5,TG group); 6% arachidonic acid(ARA) was fed to subjects for 8 weeks, and the body weight changes of mice were recorded every week. Eight weeks later, two groups of mice were put to death under anesthesia, and their liver, testis, and muscle tissues were separated on ice. The composition and level of fatty acids(FAs) in each tissue of two groups of mice were detected by gas chromatography(GC); levels of PGE_2, prostaglandin E synthase 1(PTGES1) and prostaglandin E synthase 2(PTGES2) messenger RNA relative expression in each tissue of two groups determined by enzyme-linked immunosorbent assay(ELISA) and quantitative real-time fluorescence PCR(RT-qPCR). Results From week 1 to week 8, the body mass of mice in both groups increased, and there was no significant difference between the two groups(P > 0.05). Omega-6 PUFAs(n-6 PUFAs) are the main PUFAs in WT group. Compared with WT group, ARA levels in TG group tissues decreased, levels of eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA) increased(P<0.05 or P<0.01), levels of linoleic acid(LA) increased and docosatetraenoic acid(DTA) in testis decreased(P<0.05). PGE_2 levels in testis and muscle tissue in TG group were lower than that of WT group(P<0.05 or P<0.01). The expression of PTGES1 and PTGES2 mRNA in liver and testis of TG group was lower than that of WT group(P<0.05 or P<0.01). Conclusion PUFAs can reduce the synthesis of ARA and the expression of PGE_2-related synthetase in Δ15 Des transgenic mice, thus regulating the level of PGE_2 in vivo.

关键词(KeyWords)： 花生四烯酸;脂肪酸类,不饱和;前列腺素E类;Δ15 Des转基因小鼠;多不饱和脂肪酸;前列腺素E_2;前列腺素E合酶1;前列腺素E合酶2
arachidonic acid;fatty acids,unsaturated;prostaglandins E;Δ15 Des transgenic mice;polyunsaturated fatty acids;prostaglandin E2;prostaglandin E synthase 1;prostaglandin E synthase 2

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(31960205)

作者(Author): 赵瑄,甘婷,王雨虹,巨佳曦,朱贵明
ZHAO Xuan,GAN Ting,WANG Yuhong,JU Jiaxi,ZHU Guiming

DOI: 10.19367/j.cnki.2096-8388.2023.11.004

参考文献(References)：

• [1] KANG J X.Fat-1 transgenic mice:a new model for omega-3 research[J].Prostaglandins Leukot Essent Fatty Acids,2007,77(5-6):263-267.
• [2] 华晓敏，陈俏俏，潘庆杰.FAT-1基因及其功能的研究进展[J].青岛农业大学学报(自然科学版),2012,29(1):■,et al.Omega-3 versus omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases[J].Int J Mol Sci,2020,21(3):741.
• [4] YAO C,NARUMIYA S.Prostaglandin-cytokine crosstalk in chronic inflammation[J].Br J Pharmacol,2019,176(3):337-354.
• [5] 李彧媛，张晓燕.前列腺素E2对肾脏集合管水转运的调控作用[J].生理学报，2021,73(4):681-689.
• [6] 杨光锐，管又飞.前列腺素E2合酶的研究进展[J].生理科学进展，2006(2):182-186.
• [7] AL-NAJJAR B O.Investigation of 15-hydroxyprostaglandin dehydrogenase catalytic reaction mechanism by molecular dynamics simulations[J].J Mol Graph Model,2018,80:190-196.
• [8] JANA B,CA?KA J,BULC M,et al.Role of noradrenaline and adrenoreceptors in regulating prostaglandin E2 synthesis cascade in inflamed endometrium of pigs[J].Int J Mol Sci,2023,24(6):5856.
• [9] 刘敏，郭美娜，陈丽红.前列腺素E2合酶及其受体在心血管疾病中的作用研究进展[J].生理学报，2021,73(4):665-680.
• [10]CHEN C,GUAN J,GU X,et al.Prostaglandin E2 and receptors:insight into tumorigenesis,tumor progression,and treatment of hepatocellular carcinoma[J].Front Cell Dev Biol,2022,10:834859.
• [11]RICCIOTTI E,FITZGERALD G A.Prostaglandins and inflammation[J].Arterioscler Thromb Vasc Biol,2011,31(5):986-1000.
• [12]张洪涛，单雷，毕玉平.n-6和n-3多不饱和脂肪酸在人和动物体内的功能关系[J].山东农业科学，2006,(2):115-120.
• [13]KANG J X,WANG J,WU L,et al.Transgenic mice:fat-1 mice convert n-6 to n-3 fatty acids[J].Nature,2004,427(6974):504.
• [14]杨宁，吕国栋，温浩.前列腺素E2的代谢和转运途径及其在肝再生中的作用[J].中华肝脏病杂志，2021,29(2):183-187.
• [15]WANG Z G,ZHU Z Q,HE Z Y,et al.Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids facilitates the repair of cardiotoxin-induced skeletal muscle injury in fat-1 mice[J].Aging (Albany NY),2021,13(6):8454-8466.
• [16]CALDER P C.Eicosanoids[J].Essays Biochem,2020,64(3):423-441.
• [17]陈建安，李德富，袁良，等.PGE2/EP信号通路在肺部疾病中作用的研究进展[J].国际呼吸杂志，2020,40(12):944-949.
• [18]蒋彩虹，高子蕊，郭丽凯，等.前列腺素E2在癌症发生发展中的研究进展[J].生理科学进展，2018,49(1):53-57.
• [19]OKUMURA T,SAITO K.Degradation of prostaglandin E2 in a primary culture of adult rat hepatocytes[J].J Bio Chem,1984,96(2):429-436.
• [20]陈龙，毛鑫智.花生四烯酸代谢物与肝损伤[J].中国病理生理杂志，1999(12):94-97.
• [21]GRANIER S,KIM S,SHAFER A M,et al.Structure and conformational changes in the C-terminal domain of the β2-adrenoceptor[J].J Biol Chem,2007,282(18):13895-13905.
• [22]NA Y R,JUNG D,STAKENBORG M,et al.Prostaglandin E2 receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation[J].Gut,2021,70(12):2249-2260.
• [23]CHENG H,HUANG H,GUO Z,et al.Role of prostaglandin E2 in tissue repair and regeneration[J].Theranostics,2021,11(18):8836-8854.

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