肠道细菌相关代谢产物脱氧胆酸的量效和时效对秀丽隐杆线虫生长发育的影响
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摘要
目的观察脱氧胆酸对线虫生存和生长发育的影响,了解脱氧胆酸的作用。方法实验对象分为对照组和实验组,其中实验组分为低浓度组、中浓度组和高浓度组。将L1期线虫放于实验组中培养48 h后观察不同浓度的脱氧胆酸对线虫生长的影响,在D0期(幼年成虫期)、D4期(线虫成年后第4天)、D6期(线虫成年后第6天)观察不同浓度的脱氧胆酸对线虫运动能力、抗感染能力、寿命和生殖能力的影响。结果不同浓度的脱氧胆酸对线虫生长的影响未见明显差异。在不同时间、不同浓度脱氧胆酸的作用下,线虫运动能力随着剂量的增加和时间的延长而降低,中高浓度脱氧胆酸可缩短线虫的寿命和降低抗感染能力,并呈剂量依赖性。高浓度的脱氧胆酸可以减少线虫的子代及缩短线虫的产卵时间。结论脱氧胆酸不影响线虫的生长。大剂量的脱氧胆酸对线虫可能存在量效和时效的生殖毒性作用和慢性毒性作用,缩短线虫的寿命,降低线虫的运动及抗感染能力,其作用机制仍需进一步研究。
Objective To observe the effects of deoxycholic acid on the survival and growth of Caenorhabditis elegans, and understand the role of deoxycholic acid. Methods The subjects were divided into control group and observation group. The observation group was divided into three subgroups including low concentration group, medium concentration group and high concentration group. After cultured in the observation group for 48 hours, the effects of different concentrations of deoxycholic acid on the growth of Caenorhabditis elegans were observed; the movement ability, anti-infection ability, life span and reproductive ability were observed in D_0(young adult) stage, D_4 stage(4 th day of adult) and D_6 stage(6 th day of adult). Results Deoxycholic acid did not affect the growth of Caenorhabditis elegans. With the increase of concentration and the prolongation of actuation duration, the movement ability of Caenorhabditis elegans decreased. Medium and high concentrations of deoxycholic acid shortened the life span, reduced the abilities of movement and anti-infection, reduced the progeny and shortened the spawning time of Caenorhabditis elegans. Conclusion Deoxycholic acid does not affect the growth of nematodes. High concentration of deoxycholic acid may have dose-and time-dependent reproductive toxicity and chronic toxicity to Caenorhabditis elegans, shorten the life span and reduce the abilities of movement and anti-infection, the mechanism of which should be further studied.
Objective To observe the effects of deoxycholic acid on the survival and growth of Caenorhabditis elegans, and understand the role of deoxycholic acid. Methods The subjects were divided into control group and observation group. The observation group was divided into three subgroups including low concentration group, medium concentration group and high concentration group. After cultured in the observation group for 48 hours, the effects of different concentrations of deoxycholic acid on the growth of Caenorhabditis elegans were observed; the movement ability, anti-infection ability, life span and reproductive ability were observed in D_0(young adult) stage, D_4 stage(4 th day of adult) and D_6 stage(6 th day of adult). Results Deoxycholic acid did not affect the growth of Caenorhabditis elegans. With the increase of concentration and the prolongation of actuation duration, the movement ability of Caenorhabditis elegans decreased. Medium and high concentrations of deoxycholic acid shortened the life span, reduced the abilities of movement and anti-infection, reduced the progeny and shortened the spawning time of Caenorhabditis elegans. Conclusion Deoxycholic acid does not affect the growth of nematodes. High concentration of deoxycholic acid may have dose-and time-dependent reproductive toxicity and chronic toxicity to Caenorhabditis elegans, shorten the life span and reduce the abilities of movement and anti-infection, the mechanism of which should be further studied.
引文
[1] Liu L,Dong W,Wang S,et al.Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis[J].Food Funct,2018,9(11):5588-5597.
[2] Dong W,Liu L,Dou Y,et al.Deoxycholic acid activates epidermal growth factor receptor and promotes intestinal carcinogenesis by ADAM17-dependent ligand release[J].J Cell Mol Med,2018,22(9):4263-4273.
[3] Saga K,Iwashita Y,Hidano S,et al.Secondary unconjugated bile acids induce hepatic stellate cell activation[J].Int J Mol Sci,2018,19(10):E3043.
[4] Zhao S,Gong Z,Du X,et al.Deoxycholic acid-mediated sphingosine-1-phosphate receptor 2 signaling exacerbates DSS-induced colitis through promoting cathepsin B release[J].J Immunol Res,2018,2018:2481418.
[5] Prichard DO,Byrne AM,Murphy JO,et al.Deoxycholic acid promotes development of gastroeso gastroesophageal phageal reflux disease and Barrett′s esophagus by modulating integrin-αv trafficking[J].J Cell Mol Med,2017,21(12):3612-3625.
[6] 张楠,李钰,高婷,等.人类疾病的秀丽隐杆线虫模型[C].中国环境诱变剂学会险评价专业委员会全国学术交流会,2014.
[7] 蔡金玲,杜丽,马琼,等.秀丽隐杆线虫神经免疫相互作用的研究进展[J].解放军医学杂志,2012,37(9):914-918.
[8] Stiernagle T,Maintenance of C.elegans[J].Worm Book,2006:1-11.
[9] LI Youquan,GUAN Guiquan,PENG Yulu,et al.Study on the culture and preservation of Caenorhabditis elegans[J].Chin Vet Sci,2011,41(10):1001-1004.(in Chinese) 李有全,关贵全,彭欲率,等.秀丽隐杆线虫的培养与保存研究[J].中国兽医科学,2011,41(10):1001-1004.
[10] Kakiyama G,Muto A,Takei H,et al.A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects:Validation by GC-MS and LC-MS[J].J Lipid Res,2014,55(5):978-990.
[11] Booth LA,Gilmore IT,Bilton RF.Secondary bile acid induced DNA damage in HT29cells:Are free radicals involved[J].Free Radic Res,1997,26(2):135-144.
[12] Powolny A,Xu J,Loo G.Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wildtype p53[J].Int J Biochem Cell Biol,2001,33(2):193-203.
[13] Bernstein H,Bernstein C,Payne CM,et al.Bile acids as carcinogens in human gastrointestinal cancers[J].Mutat Res,2005,589(1):47-65.
[14] WANG Haizhen,CAI Danchun,LIAO Dandan,et al.Role of endoplasmic reticulum stress-induced apoptosis of trophoblasts in intrahepatic cholestasis during pregnancy[J].J South Med Univ,2018,38(5):572-577.(in Chinese) 王海臻,蔡丹纯,廖丹丹,等.内质网应激介导滋养细胞凋亡在妊娠期肝内胆汁淤积症中的作用及机制[J].南方医科大学学报,2018,38(5):572-577.
[15] Baptissart M,Vega A,Martinot E,et al.Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice[J].Hepatology,2014,60(3):1054-1065.
[2] Dong W,Liu L,Dou Y,et al.Deoxycholic acid activates epidermal growth factor receptor and promotes intestinal carcinogenesis by ADAM17-dependent ligand release[J].J Cell Mol Med,2018,22(9):4263-4273.
[3] Saga K,Iwashita Y,Hidano S,et al.Secondary unconjugated bile acids induce hepatic stellate cell activation[J].Int J Mol Sci,2018,19(10):E3043.
[4] Zhao S,Gong Z,Du X,et al.Deoxycholic acid-mediated sphingosine-1-phosphate receptor 2 signaling exacerbates DSS-induced colitis through promoting cathepsin B release[J].J Immunol Res,2018,2018:2481418.
[5] Prichard DO,Byrne AM,Murphy JO,et al.Deoxycholic acid promotes development of gastroeso gastroesophageal phageal reflux disease and Barrett′s esophagus by modulating integrin-αv trafficking[J].J Cell Mol Med,2017,21(12):3612-3625.
[6] 张楠,李钰,高婷,等.人类疾病的秀丽隐杆线虫模型[C].中国环境诱变剂学会险评价专业委员会全国学术交流会,2014.
[7] 蔡金玲,杜丽,马琼,等.秀丽隐杆线虫神经免疫相互作用的研究进展[J].解放军医学杂志,2012,37(9):914-918.
[8] Stiernagle T,Maintenance of C.elegans[J].Worm Book,2006:1-11.
[9] LI Youquan,GUAN Guiquan,PENG Yulu,et al.Study on the culture and preservation of Caenorhabditis elegans[J].Chin Vet Sci,2011,41(10):1001-1004.(in Chinese) 李有全,关贵全,彭欲率,等.秀丽隐杆线虫的培养与保存研究[J].中国兽医科学,2011,41(10):1001-1004.
[10] Kakiyama G,Muto A,Takei H,et al.A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects:Validation by GC-MS and LC-MS[J].J Lipid Res,2014,55(5):978-990.
[11] Booth LA,Gilmore IT,Bilton RF.Secondary bile acid induced DNA damage in HT29cells:Are free radicals involved[J].Free Radic Res,1997,26(2):135-144.
[12] Powolny A,Xu J,Loo G.Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wildtype p53[J].Int J Biochem Cell Biol,2001,33(2):193-203.
[13] Bernstein H,Bernstein C,Payne CM,et al.Bile acids as carcinogens in human gastrointestinal cancers[J].Mutat Res,2005,589(1):47-65.
[14] WANG Haizhen,CAI Danchun,LIAO Dandan,et al.Role of endoplasmic reticulum stress-induced apoptosis of trophoblasts in intrahepatic cholestasis during pregnancy[J].J South Med Univ,2018,38(5):572-577.(in Chinese) 王海臻,蔡丹纯,廖丹丹,等.内质网应激介导滋养细胞凋亡在妊娠期肝内胆汁淤积症中的作用及机制[J].南方医科大学学报,2018,38(5):572-577.
[15] Baptissart M,Vega A,Martinot E,et al.Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice[J].Hepatology,2014,60(3):1054-1065.