健康及溃疡性结肠炎模型豚鼠维生素D和维生素C的交互作用
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摘要
目的探讨不同维生素D(vitamin D,VD)和维生素C(vitamin C,VC)干预水平在健康及溃疡性结肠炎(ulcerative colitis,UC)模型豚鼠VD羟化产物(25(OH)D_3、1,25(OH)_2D_3)和相关羟化酶mRNA水平上是否存在交互作用。方法将雄性Dunkin-Hartley豚鼠72只,随机分为健康组和UC模型组各36只,2组又按照VC干预3个水平[10、100、200 mg/(kg·d)]×VD干预2个水平[0.25、5μg/(kg·d)]随机分为6小组。各小组给予不同水平VD和VC灌胃干预5周后,UC模型组给予2%葡聚糖硫酸钠(DSS)自由饮用4 d进行造模,处死豚鼠,取血清和肝肾组织。检测血清25(OH)D_3、1,25 (OH)_2D_3、肝脏CYP2R1、CYP27A1及肾脏CYP27B1、CYP24A1 mRNA的表达水平。结果健康豚鼠中,血清1,25(OH)_2D_3和肾脏CYP24A1 mRNA在不同VD和VC干预水平之间存在交互作用(P<0.05);UC模型豚鼠中,在肝脏CYP27A1和肾脏CYP24A1 mRNA方面,不同VD和VC干预水平之间存在交互作用(P<0.05)。结论 VC和VD的交互作用主要影响健康豚鼠VD在肾脏的第二次羟化。
Objective To explore whether there is an interaction between different levels of vitamin D(VD) and vitamin C(VC) in hydroxylated products [25(OH)D_3, 1,25(OH)_2D_3] and related hydroxylase mRNA of healthy guinea pigs and guinea pigs suffering from ulcerative colitis(UC). Methods 72 male Dunkin-Hartley guinea pigs were randomly divided into 36 healthy group and 36 UC model group. Then the two groups were randomly divided into 6 groups according to 3 levels of VC intervention [10 mg/(kg·d), 100 mg/(kg·d), 200 mg/(kg·d)] and 2 levels of VD intervention [0.25 μg/(kg·d), 5 μg/(kg·d)].After each group was given different levels of VD and VC gavage intervention for 5 weeks, the UC model group was given2% dextran sodium sulfate(DSS) free drinking 4 d for modeling, guinea pigs were sacrificed, serum, liver and kidney samples were collected. Serum 25(OH)D_3 and 1,25(OH)_2D_3 and the mRNA expression of CYP2R1 and CYP27A1 in livers and CYP27B1 and CYP24A1 in kidneys in guinea pigs were detected. Results In healthy guinea pigs, there were interactions between different VD and VC intervention levels in serum 1,25(OH)_2D_3 and CYP24A1 mRNA expression of kidney(P<0.05).In UC model guinea pigs, there was an interaction between different VD and VC intervention levels in CYP27A1 mRNA expression of liver and CYP24A1 mRNA expression of kidney(P<0.05). Conclusion The interaction of VC and VD primarily affects the second hydroxylation in the kidney of VD of healthy guinea pig.
Objective To explore whether there is an interaction between different levels of vitamin D(VD) and vitamin C(VC) in hydroxylated products [25(OH)D_3, 1,25(OH)_2D_3] and related hydroxylase mRNA of healthy guinea pigs and guinea pigs suffering from ulcerative colitis(UC). Methods 72 male Dunkin-Hartley guinea pigs were randomly divided into 36 healthy group and 36 UC model group. Then the two groups were randomly divided into 6 groups according to 3 levels of VC intervention [10 mg/(kg·d), 100 mg/(kg·d), 200 mg/(kg·d)] and 2 levels of VD intervention [0.25 μg/(kg·d), 5 μg/(kg·d)].After each group was given different levels of VD and VC gavage intervention for 5 weeks, the UC model group was given2% dextran sodium sulfate(DSS) free drinking 4 d for modeling, guinea pigs were sacrificed, serum, liver and kidney samples were collected. Serum 25(OH)D_3 and 1,25(OH)_2D_3 and the mRNA expression of CYP2R1 and CYP27A1 in livers and CYP27B1 and CYP24A1 in kidneys in guinea pigs were detected. Results In healthy guinea pigs, there were interactions between different VD and VC intervention levels in serum 1,25(OH)_2D_3 and CYP24A1 mRNA expression of kidney(P<0.05).In UC model guinea pigs, there was an interaction between different VD and VC intervention levels in CYP27A1 mRNA expression of liver and CYP24A1 mRNA expression of kidney(P<0.05). Conclusion The interaction of VC and VD primarily affects the second hydroxylation in the kidney of VD of healthy guinea pig.
引文
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[12]Gubatan J,Mitsuhashi S,Zenlea T,et al.Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis[J].Clinical Gastroenterology and Hepatology,2017,15(2):240-246.
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[15]Garg M,Lubel JS,Sparrow MP,et al.Review article:vitamin D and inflammatory bowel disease--established concepts and future directions[J].Alimentary Pharmacology and Therapeutics,2012,36(4):324-344.
[16]张晶,冯宏娟,暴军玲,等.维生素C和维生素D水平对溃疡性结肠炎患者炎症程度的影响[J].现代预防医学,2017,44(13):2471-2474.
[17]Yan HY,Wang HJ,Zhang XL,et al.Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice[J].International Journal of Clinical and Experimental Medicine,2015,8(11):20245-20253.
[2]Dadaei T,Safapoor MH,Asadzadeh AH,et al.Effect of vitamin D3supplementation on TNF-αserum level and disease activity index in Iranian IBD patients[J].Gastroenterology and Hepatology from Bed to Bench,2015,8(1):49-55.
[3]Pappa HM,Mitchell PD,Jiang HY,et al.Maintenance of optimal vitamin D status in children and adolescents with inflammatory bowel disease:a randomized clinical trial comparing two regimens[J].Journal of Clinical Endocrinology and Metabolism,2014,99(9):3408-3417.
[4]赵建杰,朱叶珊.维生素D治疗慢性非特异性溃疡性结肠炎的疗效评价[J].山西医药杂志,2016,45(12):1424-1425.
[5]孙睿森,张晶,马莹,等.维生素C与维生素D_3联合应用对葡聚糖硫酸钠造模的豚鼠溃疡性结肠炎的改善作用[J].现代预防医学,2017,44(8):1397-1401.
[6]Seregin SS,Golovchenko N,Schaf B,et al.NLRP6 function in inflammatory monocytes reduces susceptibility to chemically-induced intestinal injury[J].Mucosal Immunology,2017,10(2):434-445.
[7]Lux-Battistelli C,Battistelli D.Latent scurvy with tiredness and leg pain in alcoholics[J].Medicine,2017,96(47):e8861.
[8]Jo'z'wiak P,Ciesielski P,Zaczek A,et al.Expression of hypoxia inducible factor 1αand 2αand its association with vitamin C level in thyroid lesions[J].Journal of Biomedical Science,2017,24:83.
[9]Guz J,Oliński R.The role of vitamin C in epigenetic regulation[J].Postepy Higieny i Medycyny Doswiadczalnej,2017,71(1):747-760.
[10]Brown RB,Haq A,Stanford CF,et al.Vitamin D,phosphate,and vasculotoxicity[J].Canadian Journal of Physiology and Pharmacology,2015,93(12):1077-1082.
[11]中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2012年·广州)[J].胃肠病学,2012,17(12):763-781.
[12]Gubatan J,Mitsuhashi S,Zenlea T,et al.Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis[J].Clinical Gastroenterology and Hepatology,2017,15(2):240-246.
[13]Christakos S,Dhawan P,Verstuyf A,et al.Vitamin D:metabolism,molecular mechanism of action,and pleiotropic effects[J].Physiological Reviews,2016,96(1):365-408.
[14]Colotta F,Jansson B,Bonelli F.Modulation of inflammatory and immune responses by vitamin D[J].Journal of Autoimmunity,2017,85(7):78-97.
[15]Garg M,Lubel JS,Sparrow MP,et al.Review article:vitamin D and inflammatory bowel disease--established concepts and future directions[J].Alimentary Pharmacology and Therapeutics,2012,36(4):324-344.
[16]张晶,冯宏娟,暴军玲,等.维生素C和维生素D水平对溃疡性结肠炎患者炎症程度的影响[J].现代预防医学,2017,44(13):2471-2474.
[17]Yan HY,Wang HJ,Zhang XL,et al.Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice[J].International Journal of Clinical and Experimental Medicine,2015,8(11):20245-20253.
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