氧化苦参碱对银屑病样模型豚鼠詹纳斯激酶/信号转导和转录激活因子信号通路的调控作用研究

Regulatory effect of oxymatrine on Janus kinase/signal transducer and transcriptional signal pathway in guinea pigs with dandruff-like disease

目的探讨氧化苦参碱对豚鼠银屑病样动物模型詹纳斯激酶(JAKs)/信号转导和转录激活因子(STATs)信号通路的调控作用。方法用5%盐酸普萘洛尔乳剂涂擦双侧耳背建立银屑病样动物模型,并随机分为模型组、对照组和低、中、高剂量实验组,每组14只;另取14只正常豚鼠用0.9%NaCl涂擦双侧耳背作为空白组。空白组灌胃给予0.9%NaCl;模型组灌胃给予0.5%羧甲基纤维素钠溶液;对照组灌胃给予0.12 mg·mL^-1阿维A混悬液;低、中、高剂量实验组分别灌胃给予0.40,0.80和1.60 mg·mL^-1氧化苦参碱混悬液。6组豚鼠给药剂量均为10 mL·kg^-1,每天给药1次,连续给药2周。比较6组皮损组织Baker组织病理学积分,皮损组织细胞因子信号转导抑制因子1(SOCS1)、JAK1和STAT3蛋白的表达水平。结果低、高剂量实验组和对照组、模型组的皮损组织Baker组织病理学积分分别为(5.42±0.71),(4.11±0.47),(3.97±0.42)和(6.58±0.69)分,SOCS1蛋白相对表达量分别为0.67±0.09,1.42±0.19,1.44±0.17和0.54±0.07,JAK1蛋白相对表达量分别为1.11±0.14,0.48±0.06,0.46±0.05和1.45±0.18,STAT3蛋白相对表达量分别为0.95±0.13,0.48±0.07,0.45±0.06和1.21±0.17,低、高剂量实验组和对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论氧化苦参碱能有效改善豚鼠银屑病样皮损,且药物浓度越高作用效果越明显,其作用可能与上调SOCS1表达,抑制JAKs/STATs信号通路激活有关。

Objective To analyze regulatory effect of oxymatrine on Janus kinase(JAKs)/signal transducer and transcriptional(STATs)signal pathway in guinea pigs with dandruff-like disease.Methods The animal model of psoriasis was established by rubbing the bilateral dorsum of ears with 5%propranolol hydrochloride emulsion,and they were randomly divided into model group,experimental-L,-M,-H groups and control group with 14 cases per group.And another 14 normal guinea pigs were smeared with 0.9%NaCl on the back of both ears as the blank group.The blank group was given 0.9%NaCl by gavage;the model group was given 0.5%carboxymethyl cellulose solution by gavage;the control group was given 0.12 mg·mL^-1 acitretin suspension by gavage;the experimental-L,-M,-H groups were given 0.40,0.80 and 1.60 mg·mL^-1 oxymatrine suspension by gavage.The guinea pigs in 6 groups were given 10 mL·kg^-1,once a day for 2 weeks.The Baker histopathological score,expression levels of cytokine signaling inhibitor 1(SOCS1),JAK1 and STAT3 proteins in skin lesions among 6 groups were detected and compared.Results The Baker histopathological scores of experimental-L,-H groups,control group and model group were(5.42±0.71),(4.11±0.47),(3.97±0.42)and(6.58±0.69)scores,the relative expression quantities of(SOCS1)protein were 0.67±0.09,1.42±0.19,1.44±0.17 and 0.54±0.07,the relative expression quantities of JAK1 protein were 1.11±0.14,0.48±0.06,0.46±0.05 and 1.45±0.18,the relative expression quantities of STAT3 protein were 0.95±0.13,0.48±0.07,0.45±0.06 and 1.21±0.17.Compared with model group,the above indexes of experimental-L,-H groups and control group were statistically significant(all P<0.05).Conclusion Oxymatrine can effectively improve the skin lesions of guinea pigs with psoriasis,and the higher the drug concentration,the more obvious the effect,which may be related to the up-regulation of SOCS1 expression and inhibition of the activation of JAKs/STATs signal pathway.