摘要
目的 探讨维生素D_(3)对溃疡性结肠炎(UC)大鼠肠道微生态、血清炎症因子水平以及Toll样受体4/髓样细胞分化因子88/转录因子-κB(TLR4/MyD88/NF-κB)信号通路的影响。方法 将大鼠分为对照组、模型组、维生素D_(3)组、美沙拉嗪组。模型组、维生素D_(3)组、美沙拉嗪组用2,4-二硝基氯苯醋酸/乙醇复合法建立UC大鼠模型,维生素D_(3)组给予胆维丁乳原液1875 U灌胃治疗,美沙拉嗪组给予10 mg·kg·d^(-1)美沙拉嗪灌胃治疗,对照组、模型组灌胃给予等量生理盐水。观察各组大鼠疾病活动指数(DAI)评分,并检测肠道菌群数量。苏木精-伊红染色观察大鼠结肠组织病理变化。气相色谱法检测肠道内容物中乙酸、丙酸、丁酸含量。酶联免疫吸附法检测血清中白细胞介素(IL)-1β、IL-6、IL-8和肿瘤坏死因子-α(TNF-α)水平。蛋白质印迹法检测结肠黏膜组织中TLR4、MyD88和NF-κB p65蛋白水平。结果 对照组、模型组、维生素D_(3)组、美沙拉嗪组大鼠DAI评分为0,(2.62±0.12),(1.49±0.09),(0.67±0.10)分;双歧杆菌数量为(12.59±1.32),(9.17±0.51),(10.88±0.99),(11.76±0.80)CFU·g^(-1);乳酸杆菌数量为(12.06±0.89),(10.04±0.99),(11.26±0.65),(12.03±0.84)CFU·g^(-1);大肠埃希菌数量为(7.99±0.56),(10.20±0.66),(8.52±0.42),(8.48±0.67)CFU·g^(-1);肠球菌数量为(8.27±0.79),(10.17±1.20),(9.26±0.54),(8.58±0.55)CFU·g^(-1);IL-1β水平为(21.89±2.10),(32.39±1.62),(25.98±1.67),(22.78±2.51)pg·mL^(-1);IL-6水平为(89.09±7.38),(134.79±20.98),(103.48±8.62),(102.45±5.68)pg·mL^(-1);TNF-α水平为(185.73±14.52),(279.85±19.42),(229.68±18.79),(208.45±22.22)pg·mL^(-1);TLR4蛋白表达水平为0.33±0.04,0.97±0.09,0.63±0.06,0.50±0.05;MyD88蛋白表达水平为0.27±0.04,0.81±0.11,0.45±0.03,0.36±0.04;NF-κB p65蛋白表达水平为0.30±0.04,1.08±0.11,0.41±0.05,0.38±0.03。以上指标,模型组与对照组比较,或维生素D_(3)组、美沙拉嗪组与模型组比较,差异均有统
Objective To explore the effect of vitamin D_(3)on intestina microecology,serum inflammatory factor levels and toll-like receptor 4/myeloid differentiation factor 88/transcription factor-κB (TLR4/MyD88/NF-κB) signaling pathway in ulcerative colitis (UC) rats.Methods Forty rats were divided into control group,model group,vitamin D_(3)group and mesalazine group.The model group,vitamin D_(3)group and mesalazine group were used to establish the UC rat model by 2,4-dinitrochlorobenzene acetic acid/ethanol composite method.The vitamin D_(3)group was treated with 1875 U bile vitin emulsion by gavage,and the mesalazine group was treated with 10 mg·kg·d^(-1)mesalazine.The conrol group and model group were give the same amount of saline.The disease activity index (DAI) score of rats in each group was observed,and the number of intestinal flora was detected.The pathological changes of colon tissue in rats were observed by hematoxylin-eosin staining.The contents of acetic acid,propionic acid and butyric acid in intestinal contents were detected by gas chromatography.Enzyme-linked immunosorbent assay detected the levels of interleukin-1β (IL-1β),IL-6,IL-8 and tumor necrosis factor-α (TNF-α) in serum.Western blot was used to detect the protein levels of TLR4,MyD88 and NF-κB p65 in colonic mucosa.Results The DAI scores of rats in the control,model,vitamin D_(3),and mesalazine groups were 0,2.62±0.12,1.49±0.09,0.67±0.10;the number of Bifidobacteria was (12.59±1.32),(9.17±0.51),(10.88±0.99),(11.76±0.80) CFU·g^(-1);the number of Lactobacilli was (12.06±0.89),(10.04±0.99),(11.26±0.65),(12.03±0.84) CFU·g^(-1);the number of Enteric bacilli were (7.99±0.56),(10.20±0.66),(8.52±0.42),(8.48±0.67) CFU·g^(-1);the numbers of Enterococcus were (8.27±0.79),(10.17±1.20),(9.26±0.54),(8.58±0.55) CFU·g^(-1);the expression levels IL-1β were (21.89±2.10),(32.39±1.62),(25.98±1.67),(22.78±2.51) pg·m L-1,and the IL-6 levels were (89.09±7.38),(134.79±20.98),(103.48±8.62),(102.45±5.68) pg·m L-1;TNF-α levels we
作者
王丹
罗纯齐
孟玲玲
彭罕鸣
WANG Dan;LUO Chun-qi;MENG Ling-ling;PENG Han-ming(Department of Gastroenterology,Wuhan Children’s Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan Maternal and Child Health Hospital,Wuhan,430015,Hubei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第2期261-265,共5页
The Chinese Journal of Clinical Pharmacology
基金
武汉市卫生健康委员会科研基金资助项目(WX21Q67)。
