摘要
目的:考察长期(3个月)应用别嘌醇缓释胶囊对高尿酸血症大鼠胃、肠和皮肤的影响及机制。方法:60只雄性Wistar大鼠随机分为正常对照(NC)组,模型(M)组,别嘌醇缓释胶囊低(CL)、高剂量(CH)组,别嘌醇片低(TL)、高剂量(TH)组,每组10只。除NC组,其余各组采用腺嘌呤(100mg·kg-1·d-1)和乙胺丁醇(250mg·kg-1·d-1)连续灌胃3周后改为隔日1次,共12周造成大鼠高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释胶囊或别嘌醇片,在实验第12周末,测量各组大鼠的体质量、血尿酸和血清白细胞介素(IL)-1β含量,胃、肠和皮肤的病理改变,及皮肤中肿瘤坏死因子(TNF)-α表达情况。结果:CH组可降低高尿酸血症大鼠血尿酸水平,缓解大鼠的体质量降低(P<0.01);与M和TL组,特别是TH组比较,CL和CH组可缓解大鼠胃、肠黏膜损伤;与M和TL组比较,CL和CH组降低大鼠血清IL-1β水平作用显著(P<0.05);CL和CH组皮肤组织中TNF-α表达明显降低。结论:与别嘌醇片比较,长期应用别嘌醇缓释胶囊在降低血尿酸的同时表现出更好的胃、肠黏膜和皮肤保护作用;抑制TNF-α及IL-1β介导的炎症反应。
Objective： To detect the effect of allopurinol sustained-release capsules （ASRC） on gastrointestinal and skin in experimental hyperuricacidemia rats by long time administration （3 months）. Methods： Sixty Wistar rats were divided into 6 groups： normal control （Nc） group, hyperuricacidemia model （M） group, ASRC treatment group （low dose, CO, ASRC treatment group （high dose, Ca）, allopurinol tablet treatment group （low dose, TL） and allopurinol tablet treatment group （high dose, T.）. Beside rats of normal group, rats in other groups were given adenine （100 mg. kg-1. d-1） and ethambutol hydrochloride（250 mg. kg-1. d-1） by continual intragastric （i.g） taking for 3 weeks and changing to administration every second day till 12 weeks. At the same time ,rats were treated with two doses of ASRC（CL, C,）, as well as allopurinol tablets （TL, T H） as control for 12 weeks. After 12-week treatment, the body mass index, content of serum uric acid, serum levels of cytokines interleukin （IL）-1β, the pathological changes of gastrointestinal and skin tissues and tumor necrosis factor （TNF）-α expression were detected in different groups. Results： The content of serum uric acid was decreased in C H group and the decreased body mass index was slowed down （P 〈 0.01）. The gastrointestinal mucosal injury was decreased in CL group and C. group than that of M, TL and T. groups. There was significant decrease in serum cytokines IL-1β in CL and Ca groups than that of M and TLgroups （P 〈 0.05）.The expression of TNF-a was significantly reduced in skin in CL and C. groups. Conclusion： Compared to allopurinol tablets, long-term taking ASRC can decrease the level of serum uric acid, protect the gastrointestinal mueosal and tissues of skin and inhibit TNF-α and IL-1β mediated inflammation response in hyperuricacidemia rats.
出处
《天津医药》
CAS
北大核心
2012年第7期701-703,I0002,共4页
Tianjin Medical Journal
