白藜芦醇对溃疡性结肠炎小鼠结肠黏膜氧化应激水平及SIRT3表达的影响
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摘要
目的研究白藜芦醇对溃疡性结肠炎(UC)小鼠结肠黏膜氧化应激水平以及乙酰化酶3(SIRT3)表达的影响。方法采用葡聚糖硫酸钠(DSS)制作UC型(MD)组、低剂量治疗组(RLD)、高剂量治疗组(RHD)。造模7 d后同时停止使用造模药物,随后RLD组及RHD组给予白藜芦醇治疗7 d,NC组及MD组给予生理盐水7 d。14 d后处死小鼠,取结肠组织行HE染色,并检测结肠黏膜中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、活性氧(ROS)活性及丙二醛(MDA)含量;采用PCR及Western blot检测SIRT3的mRNA及蛋白的表达量。结果 MD组氧化应激水平升高,SIRT3表达降低;白藜芦醇治疗后,氧化应激水平减低,SIRT3表达升高,且RHD组效果优于RLD组。结论白藜芦醇可通过上调结肠黏膜SIRT3、GSH、SOD以及下调MDA、ROS从而降低黏膜氧化应激水平,进而对UC发挥一定的治疗作用,且其效果呈剂量依赖性。
Objective To evaluate the effect of resveratrol onoxidative stress and acetylase3(SIRT3)expression in colonic musoca of mice with ulcerative colitis.MethodsUC mouse models were made by dextran sulfate sodium(DSS).There were 40 male mice and were randomly divided into four groups:normal control group(NC),model group(MD),low-dose(RLD)and high-dose(RHD)resveratrol treatment group. After 7 d,we stopped DSS treatment and gave resveratrol for another 7 d treatment at the same time. After 14 days,the mice were sacrificed and the colon tissues were harvested for HE staining. The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH),reactive oxygen species(ROS)and malondialdehyde(MDA)were tested. The SIRT3 protein expression was detected by PCR and Western-blot.ResultsIn the MD group,the level of oxidative stress was increased and SIRT3 expression was decreased. After resveratrol treatment,the level of oxidative stress was decreased and SIRT3 expression was increased. What′s more,the high-dose group was better than low-dose group.ConclusionResveratrol can up-regulate the expression of SIRT3,GSH,SOD and down-regulate MDA and ROS in colonic mucosa of ulcerative colitis,and can reduce the level of oxidative stress to some extent. The effect is dose-dependent.
Objective To evaluate the effect of resveratrol onoxidative stress and acetylase3(SIRT3)expression in colonic musoca of mice with ulcerative colitis.MethodsUC mouse models were made by dextran sulfate sodium(DSS).There were 40 male mice and were randomly divided into four groups:normal control group(NC),model group(MD),low-dose(RLD)and high-dose(RHD)resveratrol treatment group. After 7 d,we stopped DSS treatment and gave resveratrol for another 7 d treatment at the same time. After 14 days,the mice were sacrificed and the colon tissues were harvested for HE staining. The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH),reactive oxygen species(ROS)and malondialdehyde(MDA)were tested. The SIRT3 protein expression was detected by PCR and Western-blot.ResultsIn the MD group,the level of oxidative stress was increased and SIRT3 expression was decreased. After resveratrol treatment,the level of oxidative stress was decreased and SIRT3 expression was increased. What′s more,the high-dose group was better than low-dose group.ConclusionResveratrol can up-regulate the expression of SIRT3,GSH,SOD and down-regulate MDA and ROS in colonic mucosa of ulcerative colitis,and can reduce the level of oxidative stress to some extent. The effect is dose-dependent.
引文
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[2]Baltaci SB,Mogulkoc R,Baltaci AK.Resveratrol and exercise[J].Biomed Rep,2016,5(5):525.
[3]Samsamikor M,Daryani NE,Asl PR,et al.Resveratrol supplementation and oxidative/anti-oxidative status in patients with ulcerative colitis:a randomized,double-blind,placebo-controlled pilot study[J].Arch Med Res,2016,47(4):304-309.
[4]顾怡康,王艺宙,胥加龙,王慧.白藜芦醇治疗溃疡性结肠炎的机制研究进展[J].药物生物技术,2017,24(1):72-75.
[5]王国恩,翟羽佳,何蓉蓉,等.SirT3调节氧化应激作用[J].中国药理学通报,2012,28(10):1333-1336.
[6]Wang XX,Edelstein MH,Gafter U,et al.G Protein-coupled bile acid receptor TGR5 activation inhibits kidney disease in obesity and diabetes[J].J Am Soc Nephrol,2016,27(5):1362-1378.
[7]Yamamoto T,Shimoyama T,Moeko Kuriyama MDietary and enteral interventions for Crohn′s disease[J].Current Opin Biotechnol,2017,44:69-73.
[8]Wang ZQ,Li S,Cao Y,et al.Oxidative stress and carbonyl lesions in ulcerative colitis and associated colorectal cancer[J].Oxidative Medicine and Cellular Longevity,2015,2016(3):1-15.
[9]姚君,王立生,王建尧,等.白藜芦醇对溃疡性结肠炎小鼠肠黏膜细胞因子表达的影响[J].中药新药与临床药理,2010,21(3):227-230.
[10]姚君,王立生,李迎雪,等.白藜芦醇对溃疡性结肠炎小鼠外周血和肠系膜淋巴结CD4+CD25+Foxp3+调节T淋巴细胞表达的影响[J].世界华人消化杂志,2010,18(27):2905-2908.
[11]Howitz KT,Bitterman KJ,Cohen HY,et al.Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan[J].Nature,2003,425(6954):191-196.