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目的探讨褪黑激素(MT)对哮喘大鼠的防治作用及可能机制。方法56只健康雌性SD大鼠随机分成7组,每组8只。用卵清蛋白建立哮喘大鼠模型。MT大剂量组(T1组)、MT中剂量组(T2组)、MT小剂量组(T3组)和地塞米松(DXM)组(D组)分别于雾化前0.5 h腹腔注射MT水溶液0.1、1、10 mg·k~(-1),DXM水溶液0.5 mg·kg~(-1);哮喘模型组(B组)给予等量生理盐水。正常对照组(A1组)和正常用药组(A2组)在造模时给予等量生理盐水替代,A2组于每次雾化前0.5 h腹腔注射MT水溶液0.1 mg·kg~(-1)。计数外周血嗜酸粒细胞(EOS)百分比、肺泡灌洗液(BALF)中炎症细胞总数、每高倍镜视野下气道周围EOS数目,流式细胞术检测外周血中CD4~+CD25~+调节性T细胞(CD4~+CD25~+Tr)数目变化。结果(1)与A1组相比,A2组外周血EOS百分比、BALF炎症细胞总数及每高倍镜视野下气道周围EOS数目无差异(均P>0.05)。与B组相比,T1、T2、T3和D组气道上述指标呈不同程度降低或降至正常。(2)与A1组相比,A2、B、T1和T2组大鼠外周血中CD4~+CD25~+Tr/CD4~+T百分比均升高,而各治疗组与B组相比有不同程度降低。结论MT对CD4~+CD25~+Tr的调节作用可能是减轻哮喘大鼠气道炎性的机制之一,其对CD4~+CD25~+Tr的影响与MT的使用剂量和大鼠机体的免疫状态均有关。
Objective To investigate the preventive and therapeutic effects of melatonin (MT) on asthmatic rats and its possible mechanism. Methods 56 healthy female SD rats were randomly divided into 7 groups with 8 in each group. Asthma rat model was established with ovalbumin. MT high dose group (T1 group), MT medium dose group (T2 group), MT low dose group (T3 group) and dexamethasone group (D group) , 1, 10 mg · k -1, DXM 0.5 mg · kg -1. The asthmatic model group (group B) received the same amount of saline. The normal control group (group A1) and the normal control group (group A2) were given the same amount of saline instead of the normal control group. In the A2 group, intraperitoneal injection of 0.1 mg · kg ~ (-1) MT 0.5 h prior to each atomization. The percentage of peripheral blood eosinophils (EOS), the total number of inflammatory cells in BALF, the number of EOS around the perimetric system at each high magnification were measured. The levels of CD4 ~ + CD25 + in peripheral blood were measured by flow cytometry T cell (CD4 ~ + CD25 ~ + Tr) changes in the number. Results (1) Compared with group A1, there was no difference in the percentage of EOS in peripheral blood A2 group, the total number of inflammatory cells in BALF and the number of EOS around the peri-airway in A2 group (all P> 0.05). Compared with the B group, T1, T2, T3 and D groups of airway in the above indicators were reduced to some extent or reduced to normal. (2) Compared with A1 group, the percentage of CD4 ~ + CD25 ~ + Tr / CD4 ~ + T in peripheral blood of A2, B, T1 and T2 groups were all increased Decreased. Conclusion The regulatory effect of MT on CD4 ~ + CD25 ~ + Tr may be one of the mechanisms of alleviating airway inflammation in asthmatic rats. The effect of MT on CD4 ~ + CD25 ~ + Tr and the dose of MT and the immunity of rat Status is related.