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全反式维甲酸对哮喘模型大鼠Th1/Th2平衡的影响

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[目的]观察不同剂量全反式维甲酸(All-trans retinoid acid,ATRA)对哮喘模型大鼠Th1/Th2平衡的影响。[方法]将SD大鼠随机分为对照组、模型组、低剂量组、中剂量组和高剂量组。对照组和模型组的大鼠给予生理盐水(10 mL/kg)灌胃,对低/中/高剂量组的大鼠,分别给予10 mg/kg、20 mg/kg和40 mg/kg ATRA灌胃,1次/d,持续1 w。观察各组大鼠的肺功能、肺组织匀浆液细胞因子水平、血Th1/Th2值及Notch通路的表达情况。[结果]中/高剂量组大鼠呼吸频率显著低于模型组(P<0。05);吸气流量、呼气峰流量和潮气量显著高于模型组(P<0。05);模型组、低/中/高剂量组肺组织匀浆液中的IgE、IL-4和IL-5水平依次降低,IFN-γ和IL-12水平依次升高;模型组Th1/Th2值显著高于对照组(P<0。05),ATRA治疗后Th1/Th2值较模型组均显著降低,剂量越高Th1/Th2值降低越明显;与对照组相比,模型组、低/中/高剂量组的Notch3、Delta1、Jagged1和Jagged2的mRNA和蛋白表达水平升高,且模型组高于低/中/高剂量组。[结论]ATRA可改善哮喘模型大鼠肺功能,调节Th1/Th2平衡,其机制可能与ATRA抑制Notch通路有关。
Effects of all-trans retinoic acid on Th1/Th2 balance in asthmatic rat models
[Objective]To observe the effects of different doses of All-trans retinoid acid(ATRA)on Th1/Th2 balance of asthmatic rats.[Method]SD rats were randomly divided into control group,model group,low-dose/medium-dose/high-dose group.Rats in control group and model group were given normal saline(10 mL/kg)by gavage,and rats in low-dose,me-dium-dose and high-dose groups were given ATRA by gavage at 10 mg/kg,20 mg/kg and 40 mg/kg,once a day for 1 week,lung function,cytokine level in lung tissue homogenate,Th 1/Th2 value in venous blood and Notch pathway expression were ob-served in each group.[Result]The respiratory rate of rats in medium/high dose group were significantly lower than that in model group(P<0.05),inspiratory flow,peak expiratory flow and tidal volume were significantly higher than model group(P<0.05);IgE,IL-4 and IL-5 levels in the homogenate of lung tissue in model group and low/medium/high dose groups were decreased successively,while IFN-γ and IL-12 levels were increased successively;Th1/Th2 ratio of the model group was significantly higher than that control group(P<0.05),after ATRA treatment,Th 1/Th2 ratio was significantly decreased com-pared with model group,and the higher the dose was,the more obvious the decrease was.Compared with control group,mRNA and protein expression levels of Notch3,Delta1,Jagged1 and Jagged2 in model group and low/medium/high dose group were in-creased,and model group was higher than low/medium/high dose group.[Conclusion]ATRA can improve the respiratory func-tion and regulate the balance of Th1/Th2 in asthmatic rats.The mechanism may be related to the inhibition of Notch pathway by ATRA.

all-trans retinoid acidNotch signaling pathwayratsTh1/Th2

林宏、陈文锋

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上海市静安区闸北中心医院呼吸与危重症医学科,上海 200070

全反式维甲酸 Notch信号通路 大鼠 Th1/Th2

上海市科技创新行动计划自然科学研究项目上海市科研计划

20ZR145040018140904000

2024

生物技术
黑龙江省微生物学会 黑龙江省生物工程学会 黑龙江省科学院微生物研究所

生物技术

CSTPCD
影响因子:0.611
ISSN:1004-311X
年,卷(期):2024.34(1)
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