维生素D水平与炎症性肠病及其作用机制的相关研究
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摘要
炎症性肠病(inflammatory bowel disease, IBD)是以反复发作的慢性肠道炎症为特点的一组疾病,主要包括溃疡性结肠炎(ulcerative colitis, UC)和克罗恩病(crohn's disease, CD)。目前认为,IBD是以遗传易感性为基础,环境因素参与,粘膜免疫系统对肠腔内抗原物质(如共生菌)的异常免疫应答而造成肠道损伤。
近年发现维生素D(vitamin D, VitD)除传统调节钙、磷代谢的作用外,对抗感染和调节免疫具有广泛作用。VitD可以调节免疫系统发育和功能,其活性形式通过直接或间接抑制IBD致病T细胞的功能,诱导抑制IBD发展的调节T细胞而发挥作用,因而可能对IBD的发病产生影响。同时,IBD患者易发生骨量减少/骨质疏松,导致骨折风险明显升高,严重影响患者生活质量,VitD对骨代谢存在调节作用。VitD与IBD的关系日渐受到关注。本研究旨在：
1、探讨我国IBD患者血清25(OH)D3水平、骨代谢状况以及与IBD病情程度的关系,分析其危险因素；评估补充VitD对改善VitD缺乏、骨代谢状况和IBD病情程度的干预治疗效果。
2、通过三硝基苯磺酸(TNBS)诱导的大鼠实验性结肠炎模型,探讨不同剂量VitD对T细胞免疫的可能调节机制。
第一部分我国炎症性肠病患者维生素D水平与骨代谢相关研究
目的：探讨我国IBD患者血清25(OH)D3水平、骨代谢状况以及与IBD病情程度的关系,分析其危险因素；评估补充VitD对改善VitD缺乏、骨代谢状况和IBD病情程度的干预治疗效果。
方法：
1.收集107例溃疡性结肠炎(UC)患者、105例克罗恩病(CD)患者及160例正常对照人群的临床资料和血清25(OH)D3水平,IBD患者检测骨密度。
2.212例IBD患者中初始骨密度降低者随机分为钙剂组、钙剂+VitD3组,初始骨密度正常者随机分为钙剂组、钙剂+VitD3组和对照组,其中钙剂为每日摄入钙600mg, VitD3为每3月摄入VitD350000IU,第3月、第6月、第12月随访,评估Mayo指数／简化CDAI评分、病情分期,检测血清25(OH)D3水平,并于第12月复查骨密度。
结果：
1.UC组血清25(OH)D3水平均较正常组明显降低(10.55±4.27VS12.89±5.32,P<0.001),CD组血清25(OH)D3水平均较正常组明显降低(11.53±4.84VS12.89±5.32,P=0.040)。UC患者血清25(OH)D3水平与病情程度呈负相关(r=-0.337,P<0.001)；CD患者血清25(OH)D3水平与病情程度呈负相关(r=-0.387,P<0.001)。UC患者骨量减少和骨质疏松的发病率分别为45.8%和2.8%,CD患者骨量减少和骨质疏松的发病率分别为38.1%和5.7%。糖皮质激素累积量是UC患者(OR=1.219,95%CI1.054～1.410,P=0.008)和CD患者(OR=1.288,95%CI1.033～1.606,P=0.025)发生骨量减少/骨质疏松的危险因素。
2.UC和CD患者补充VitD组血清25(OH)D3水平1年后升高程度明显高于未补充VitD组(P<0.001)；股骨颈、全髋和腰椎L1-4骨密度改善均值高于未补充VitD组,但未达到统计学差异(P>0.05)；Mayo评分／简化CDAI评分下降程度也无明显统计学差异(P>0.05)。
结论：IBD患者存在血清25(OH)D3水平缺乏且与病情程度相关；IBD患者易出现骨量减少／骨质疏松,糖皮质激素累积量是其危险因素；补充VitD可明显提高血清25(OH)D3水平,骨密度均值有所提高但未能达到统计学差异,未发现对IBD病情的明显改善作用。
第二部分维生素D3对三硝基苯磺酸诱导的大鼠结肠炎的作用
研究目的；探讨不同剂量维生素D3对三硝基苯磺酸(TNBS)诱导的大鼠结肠炎的疗效及机制。
研究方法：
1、建立TNBS实验性结肠炎模型及药物干预分组：54只雄性SD大鼠随机分为9组(n=6),除空白对照组外,其余8组均给予TNBS灌肠,造模后24小时药物灌胃干预,5-ASA组[每日0.40g/(kg·d)×9日]、常规剂量VitD3(第1日1800UVitD3)、单次大剂量VitD3(第1日7500U VitD3)和连续大剂量VitD3(每日7500UVitD3×9日),以及常规剂量VitD3+5-ASA组、单次大剂量VitD3+5-ASA组、连续大剂量VitD3+5-ASA组。
2、疗效评价：大鼠TNBS造模后评估疾病活动指数(DAI),第10天处死大鼠取结肠组织评估大体形态损伤评分、病理组织学评分和测定髓过氧化物酶(MPO)活性。
3、免疫机制研究：ELISA法检测结肠组织匀浆白细胞介素(IL)-2、IL-17、干扰素(IFN)-γ,反转录聚合酶链反应(RT-PCR)法检测结肠T-bet、GATA-3水平。
结果：
1、TNBS组DAI评分、大体损伤评分、组织病理学评分、MPO活性均明显高于空白对照组(P<0.001)；单次和连续大剂量VitD3联合5-ASA组大体损伤评分和组织病理学评分较TNBS组明显下降(P<0.05)；各药物干预组MPO活性均较TNBS组明显下降(P值均<0.001)。连续大剂量VitD3组和其联合5-ASA组大鼠出现高钙血症,且连续大剂量VitD3组血肌酐水平明显高于其它各组(P<0.05)。
2. IL-2、IFN-γ水平在各组中无统计学差异(P>0.05)；IL-17水平在常规剂量VitD3组明显低于TNBS组、5-ASA组(P<0.05)。T-bet在空白组无表达,在TNBS组弱表达,5-ASA组、单次大剂量VitD3组和其联合5-ASA组、连续大剂量VitD3组和其联合5-ASA组均表达减少至缺失。GATA-3在5-ASA组、连续大剂量VitD3组较TNBS组明显升高(P<0.05)。
结论：VitD3可通过调节T细胞免疫减轻TNBS诱导的实验性结肠炎。
Inflammatory bowel disease (IBD) is a group of diseases characterized by chronically recurrent episodes of intestinal inflammation, and includes ulcerative colitis (UC) and Crohn's disease (CD). The etiology of IBD is complex, and includes genetic susceptibility, environmental factors, and abnormal mucosal immune responses to antigenic material in the gut, such as the symbiotic bacteria.
It has been shown that vitamin D (VitD) has anti-inflammatory, anti-cancer and immune regulatory effects, in addition to its traditional role regulating calcium and phosphorus metabolism. Vit D can modulate the immune system development and function, its active form can directly or indirectly inhibit the function of the IBD pathogenic T cells, induce regulatory T cells which can suppress the development of IBD, then have an impact on the incidence of IBD. IBD patients prone to have bone loss/osteoporosis, resulting in significantly higher risk of fracture, seriously affect the life quality of IBD patients. Vit D plays the role of regulatory on bone metabolism. The relationship between Vit D and IBD is becoming increasingly concerned. Therefore, we aim to:
1. Explore serum25(OH) D3levels, bone metabolism status and the relationship with IBD disease activity in Chinese IBD patients, analyze the risk factors; asses the intervention treatment effects of supplying VitD on25(OH) D3levels, bone metabolism status and IBD severity.
2. Explore the regulation effects of different doses vitamin D on T cell immunity regulation in rats with experimental colitis induced by trinitrobenzene sulfonic acid (TNBS) model.
Part1. Vitamin D Levels and Bone Metabolism in Chinese Adult Patients with Inflammatory Bowel Disease.
Objective:Explore serum25(OH) D3levels, bone metabolism status and the relationship with IBD disease activity in Chinese IBD patients, analyze the risk factors; asses the intervention treatment effects of supplying VitD on25(OH) D3levels, bone metabolism status and IBD severity.
Methods:
1. The clinical data of107ulcerative colitis (UC) patients,105Crohn's disease (CD) patients and160normal controls, were collected. The serum25(OH) D3levels, the bone mineral density of IBD patients were measured.
2.212IBD patients with initially osteopenia/osteoporosis were randomized into the calcium supplement or calcium and vitamin D supplemental group. IBD patients with normal BMD were randomized into placebo, calcium supplement, or calcium and vitamin D supplemental groups. Calcium supplement group paitents take calcium600mg per day, vitamin D supplemental group patients take VitD350000IU per3months. All patients were followed on3months,6months and12months for Mayo index/simplify CDAI score, serum25(OH) D3levels, and BMD at12months intervals.
Results:
1. Serum25(OH) D3levels of UC patients were significant decreased than nrmal control group (10.55±4.27VS12.89±5.32, P<0.001), also the serum25(OH) D3levels of CD patients were significant decreased than nrmal control group (11.53±4.84VS12.89±5.32, P=0.040). Within the UC group, serum25(OH) D3levels was negatively correlated with the IBD severity (r=-0.337, P<0.001). Within the UC group,25(OH) D3levels were negatively and significantly correlated with disease severity (r=-0.387, P<0.001). Similar results were also observed within the CD group (r=-0.285, p=0.030). The prevalence of osteopenia and osteoporosis were high in IBD patients (45.8%and2.8%, respectively, in UC; and38.1%and5.7%, respectively, in CD). Cumulative quantities of glucocorticoid use was significantly associated with osteopenia/osteoporosis in both UC (OR=1.219,95%CI1.054-1.410, p=0.008) and CD (OR=1.288,95%CI1.033-1.606, p=0.025) patients.
2. The elevated25(OH) D3levels of VitD supplement group in UC and CD patients were obviously higher than the no VitD supplement group after1year (P<0.001); the mean improvement levels of femoral neck, femur and lumbar1-4bone mineral density were higher in VitD supplement group, but did not reach statistical significance (P>0.05); the Mayo score/simplify CDAI score decreased degree was no significant difference between2groups (P>0.05).
Conclusions:IBD patients were found to have25(OH) D3deficiencies that correlate with the IBD severity; IBD patients prone to have osteopenia/osteoporosis, the cumulative amount of glucocorticoid was a risk factor; supplemental VitD can significantly increase serum25(OH) D3levels, but did not find a significant improvement in BMD and IBD severity.
Part2. Effects of vitamin D on trinitrobenzene sulfonic acid induced colitis in rats.
Objective:Explore the effects of different doses vitamin D in rats with experimental colitis induced by trinitrobenzene sulfonic acid (TNBS).
Methods:
1. Establishment of TNBS experimental colitis model and drug intervention grouping:54SD rats were randomly divided into9groups (n=6), in addition to the normal control group, experimental colitis of remaining8groups were induced by enema administration of TNBS. After24hours, drug intervention was done by gavage.5-ASA group [daily0.40g/(kg·d)], conventional dose of VitD3group(lst day1800UVitD3), single high dose of VitD3group(lst day7500U VitD3) and continuous high dose of VitD3group (daily7500UVitD3), and conventional dose of VitD3+5-ASA group, single high doses of VitD3+5-ASA group, continuous high dose of VitD3+5-ASA group.
2. Evaluation of therapeutic effect:Assess disease activity index (DAI) score after establishment of TNBS experimental colitis model, all rats were sacrificed the10th day and assessed disease activity index (DAI), macroscopic lesion, histological damage score, the activity of myeloperoxidase (MPO) was measured.
3. Immune Mechanism:Detected interleukin (IL)-2, IL-17and IFN-y of colonic tissue homogenates by ELISA, colon T-bet and GATA-3level by reverse transcription polymerase chain reaction (RT-PCR).
Results:
1. DAI score, anatomical lesion score, histopathology score, MPO activity of TNBS group were significantly higher than the normal control group (P<0.001). Compared with TNBS group, macroscopic injury score and histological score in single high dose and continuous high dose VitD3combined with5-ASA groups were significantly decreased (P<0.05); MPO activity in all drugs intervention groups was decreased significantly (P<0.001). Rats in continuous high dose VitD3group and combined with5-ASA group had hypercalcemia, and serum level of creatinine in continuous high dose VitD3group was significantly increased than all the other groups (P<0.05).
2. The levels of IL-2and IFN-y in each group had no significant difference (P>0.05). IL-17levels in conventional dose of VitD3group was significantly lower than the TNBS group,5-ASA group (P<0.05). No T-bet expression in normal control group, weak expression in TNBS group,5-ASA group, single high dose of VitD3group, continuous high dose of VitD3group and combined with5-ASA group decreased to missing. GATA-3mRNA expression in5-ASA group, continuous high dose VitD3group was significantly increased compared to TNBS group (P=0.037and0.035, respectively).
Conclusions:VitD3can alleviate TNBS induced experimental colitis by regulating T cell immunity.
近年发现维生素D(vitamin D, VitD)除传统调节钙、磷代谢的作用外,对抗感染和调节免疫具有广泛作用。VitD可以调节免疫系统发育和功能,其活性形式通过直接或间接抑制IBD致病T细胞的功能,诱导抑制IBD发展的调节T细胞而发挥作用,因而可能对IBD的发病产生影响。同时,IBD患者易发生骨量减少/骨质疏松,导致骨折风险明显升高,严重影响患者生活质量,VitD对骨代谢存在调节作用。VitD与IBD的关系日渐受到关注。本研究旨在：
1、探讨我国IBD患者血清25(OH)D3水平、骨代谢状况以及与IBD病情程度的关系,分析其危险因素；评估补充VitD对改善VitD缺乏、骨代谢状况和IBD病情程度的干预治疗效果。
2、通过三硝基苯磺酸(TNBS)诱导的大鼠实验性结肠炎模型,探讨不同剂量VitD对T细胞免疫的可能调节机制。
第一部分我国炎症性肠病患者维生素D水平与骨代谢相关研究
目的：探讨我国IBD患者血清25(OH)D3水平、骨代谢状况以及与IBD病情程度的关系,分析其危险因素；评估补充VitD对改善VitD缺乏、骨代谢状况和IBD病情程度的干预治疗效果。
方法：
1.收集107例溃疡性结肠炎(UC)患者、105例克罗恩病(CD)患者及160例正常对照人群的临床资料和血清25(OH)D3水平,IBD患者检测骨密度。
2.212例IBD患者中初始骨密度降低者随机分为钙剂组、钙剂+VitD3组,初始骨密度正常者随机分为钙剂组、钙剂+VitD3组和对照组,其中钙剂为每日摄入钙600mg, VitD3为每3月摄入VitD350000IU,第3月、第6月、第12月随访,评估Mayo指数／简化CDAI评分、病情分期,检测血清25(OH)D3水平,并于第12月复查骨密度。
结果：
1.UC组血清25(OH)D3水平均较正常组明显降低(10.55±4.27VS12.89±5.32,P<0.001),CD组血清25(OH)D3水平均较正常组明显降低(11.53±4.84VS12.89±5.32,P=0.040)。UC患者血清25(OH)D3水平与病情程度呈负相关(r=-0.337,P<0.001)；CD患者血清25(OH)D3水平与病情程度呈负相关(r=-0.387,P<0.001)。UC患者骨量减少和骨质疏松的发病率分别为45.8%和2.8%,CD患者骨量减少和骨质疏松的发病率分别为38.1%和5.7%。糖皮质激素累积量是UC患者(OR=1.219,95%CI1.054～1.410,P=0.008)和CD患者(OR=1.288,95%CI1.033～1.606,P=0.025)发生骨量减少/骨质疏松的危险因素。
2.UC和CD患者补充VitD组血清25(OH)D3水平1年后升高程度明显高于未补充VitD组(P<0.001)；股骨颈、全髋和腰椎L1-4骨密度改善均值高于未补充VitD组,但未达到统计学差异(P>0.05)；Mayo评分／简化CDAI评分下降程度也无明显统计学差异(P>0.05)。
结论：IBD患者存在血清25(OH)D3水平缺乏且与病情程度相关；IBD患者易出现骨量减少／骨质疏松,糖皮质激素累积量是其危险因素；补充VitD可明显提高血清25(OH)D3水平,骨密度均值有所提高但未能达到统计学差异,未发现对IBD病情的明显改善作用。
第二部分维生素D3对三硝基苯磺酸诱导的大鼠结肠炎的作用
研究目的；探讨不同剂量维生素D3对三硝基苯磺酸(TNBS)诱导的大鼠结肠炎的疗效及机制。
研究方法：
1、建立TNBS实验性结肠炎模型及药物干预分组：54只雄性SD大鼠随机分为9组(n=6),除空白对照组外,其余8组均给予TNBS灌肠,造模后24小时药物灌胃干预,5-ASA组[每日0.40g/(kg·d)×9日]、常规剂量VitD3(第1日1800UVitD3)、单次大剂量VitD3(第1日7500U VitD3)和连续大剂量VitD3(每日7500UVitD3×9日),以及常规剂量VitD3+5-ASA组、单次大剂量VitD3+5-ASA组、连续大剂量VitD3+5-ASA组。
2、疗效评价：大鼠TNBS造模后评估疾病活动指数(DAI),第10天处死大鼠取结肠组织评估大体形态损伤评分、病理组织学评分和测定髓过氧化物酶(MPO)活性。
3、免疫机制研究：ELISA法检测结肠组织匀浆白细胞介素(IL)-2、IL-17、干扰素(IFN)-γ,反转录聚合酶链反应(RT-PCR)法检测结肠T-bet、GATA-3水平。
结果：
1、TNBS组DAI评分、大体损伤评分、组织病理学评分、MPO活性均明显高于空白对照组(P<0.001)；单次和连续大剂量VitD3联合5-ASA组大体损伤评分和组织病理学评分较TNBS组明显下降(P<0.05)；各药物干预组MPO活性均较TNBS组明显下降(P值均<0.001)。连续大剂量VitD3组和其联合5-ASA组大鼠出现高钙血症,且连续大剂量VitD3组血肌酐水平明显高于其它各组(P<0.05)。
2. IL-2、IFN-γ水平在各组中无统计学差异(P>0.05)；IL-17水平在常规剂量VitD3组明显低于TNBS组、5-ASA组(P<0.05)。T-bet在空白组无表达,在TNBS组弱表达,5-ASA组、单次大剂量VitD3组和其联合5-ASA组、连续大剂量VitD3组和其联合5-ASA组均表达减少至缺失。GATA-3在5-ASA组、连续大剂量VitD3组较TNBS组明显升高(P<0.05)。
结论：VitD3可通过调节T细胞免疫减轻TNBS诱导的实验性结肠炎。
Inflammatory bowel disease (IBD) is a group of diseases characterized by chronically recurrent episodes of intestinal inflammation, and includes ulcerative colitis (UC) and Crohn's disease (CD). The etiology of IBD is complex, and includes genetic susceptibility, environmental factors, and abnormal mucosal immune responses to antigenic material in the gut, such as the symbiotic bacteria.
It has been shown that vitamin D (VitD) has anti-inflammatory, anti-cancer and immune regulatory effects, in addition to its traditional role regulating calcium and phosphorus metabolism. Vit D can modulate the immune system development and function, its active form can directly or indirectly inhibit the function of the IBD pathogenic T cells, induce regulatory T cells which can suppress the development of IBD, then have an impact on the incidence of IBD. IBD patients prone to have bone loss/osteoporosis, resulting in significantly higher risk of fracture, seriously affect the life quality of IBD patients. Vit D plays the role of regulatory on bone metabolism. The relationship between Vit D and IBD is becoming increasingly concerned. Therefore, we aim to:
1. Explore serum25(OH) D3levels, bone metabolism status and the relationship with IBD disease activity in Chinese IBD patients, analyze the risk factors; asses the intervention treatment effects of supplying VitD on25(OH) D3levels, bone metabolism status and IBD severity.
2. Explore the regulation effects of different doses vitamin D on T cell immunity regulation in rats with experimental colitis induced by trinitrobenzene sulfonic acid (TNBS) model.
Part1. Vitamin D Levels and Bone Metabolism in Chinese Adult Patients with Inflammatory Bowel Disease.
Objective:Explore serum25(OH) D3levels, bone metabolism status and the relationship with IBD disease activity in Chinese IBD patients, analyze the risk factors; asses the intervention treatment effects of supplying VitD on25(OH) D3levels, bone metabolism status and IBD severity.
Methods:
1. The clinical data of107ulcerative colitis (UC) patients,105Crohn's disease (CD) patients and160normal controls, were collected. The serum25(OH) D3levels, the bone mineral density of IBD patients were measured.
2.212IBD patients with initially osteopenia/osteoporosis were randomized into the calcium supplement or calcium and vitamin D supplemental group. IBD patients with normal BMD were randomized into placebo, calcium supplement, or calcium and vitamin D supplemental groups. Calcium supplement group paitents take calcium600mg per day, vitamin D supplemental group patients take VitD350000IU per3months. All patients were followed on3months,6months and12months for Mayo index/simplify CDAI score, serum25(OH) D3levels, and BMD at12months intervals.
Results:
1. Serum25(OH) D3levels of UC patients were significant decreased than nrmal control group (10.55±4.27VS12.89±5.32, P<0.001), also the serum25(OH) D3levels of CD patients were significant decreased than nrmal control group (11.53±4.84VS12.89±5.32, P=0.040). Within the UC group, serum25(OH) D3levels was negatively correlated with the IBD severity (r=-0.337, P<0.001). Within the UC group,25(OH) D3levels were negatively and significantly correlated with disease severity (r=-0.387, P<0.001). Similar results were also observed within the CD group (r=-0.285, p=0.030). The prevalence of osteopenia and osteoporosis were high in IBD patients (45.8%and2.8%, respectively, in UC; and38.1%and5.7%, respectively, in CD). Cumulative quantities of glucocorticoid use was significantly associated with osteopenia/osteoporosis in both UC (OR=1.219,95%CI1.054-1.410, p=0.008) and CD (OR=1.288,95%CI1.033-1.606, p=0.025) patients.
2. The elevated25(OH) D3levels of VitD supplement group in UC and CD patients were obviously higher than the no VitD supplement group after1year (P<0.001); the mean improvement levels of femoral neck, femur and lumbar1-4bone mineral density were higher in VitD supplement group, but did not reach statistical significance (P>0.05); the Mayo score/simplify CDAI score decreased degree was no significant difference between2groups (P>0.05).
Conclusions:IBD patients were found to have25(OH) D3deficiencies that correlate with the IBD severity; IBD patients prone to have osteopenia/osteoporosis, the cumulative amount of glucocorticoid was a risk factor; supplemental VitD can significantly increase serum25(OH) D3levels, but did not find a significant improvement in BMD and IBD severity.
Part2. Effects of vitamin D on trinitrobenzene sulfonic acid induced colitis in rats.
Objective:Explore the effects of different doses vitamin D in rats with experimental colitis induced by trinitrobenzene sulfonic acid (TNBS).
Methods:
1. Establishment of TNBS experimental colitis model and drug intervention grouping:54SD rats were randomly divided into9groups (n=6), in addition to the normal control group, experimental colitis of remaining8groups were induced by enema administration of TNBS. After24hours, drug intervention was done by gavage.5-ASA group [daily0.40g/(kg·d)], conventional dose of VitD3group(lst day1800UVitD3), single high dose of VitD3group(lst day7500U VitD3) and continuous high dose of VitD3group (daily7500UVitD3), and conventional dose of VitD3+5-ASA group, single high doses of VitD3+5-ASA group, continuous high dose of VitD3+5-ASA group.
2. Evaluation of therapeutic effect:Assess disease activity index (DAI) score after establishment of TNBS experimental colitis model, all rats were sacrificed the10th day and assessed disease activity index (DAI), macroscopic lesion, histological damage score, the activity of myeloperoxidase (MPO) was measured.
3. Immune Mechanism:Detected interleukin (IL)-2, IL-17and IFN-y of colonic tissue homogenates by ELISA, colon T-bet and GATA-3level by reverse transcription polymerase chain reaction (RT-PCR).
Results:
1. DAI score, anatomical lesion score, histopathology score, MPO activity of TNBS group were significantly higher than the normal control group (P<0.001). Compared with TNBS group, macroscopic injury score and histological score in single high dose and continuous high dose VitD3combined with5-ASA groups were significantly decreased (P<0.05); MPO activity in all drugs intervention groups was decreased significantly (P<0.001). Rats in continuous high dose VitD3group and combined with5-ASA group had hypercalcemia, and serum level of creatinine in continuous high dose VitD3group was significantly increased than all the other groups (P<0.05).
2. The levels of IL-2and IFN-y in each group had no significant difference (P>0.05). IL-17levels in conventional dose of VitD3group was significantly lower than the TNBS group,5-ASA group (P<0.05). No T-bet expression in normal control group, weak expression in TNBS group,5-ASA group, single high dose of VitD3group, continuous high dose of VitD3group and combined with5-ASA group decreased to missing. GATA-3mRNA expression in5-ASA group, continuous high dose VitD3group was significantly increased compared to TNBS group (P=0.037and0.035, respectively).
Conclusions:VitD3can alleviate TNBS induced experimental colitis by regulating T cell immunity.
引文
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