刺山柑总生物碱对系统性硬皮病小鼠皮肤纤维化相关指标的影响

Effect of capparis spinosa total alkaloid on skin fibrosis related indexes in mice with systemic sclerosis

目的研究刺山柑总生物碱对系统性硬皮病(SSc)小鼠Ⅰ型胶原α1链(COL1A1)、纤维连接蛋白(Fn)、血管紧张素Ⅱ(AngⅡ)和白细胞介素-1β(IL-1β)等皮肤纤维化相关指标的影响。方法 90只BALB/c小鼠随机分为对照组、模型组、青霉胺组及刺山柑总生物碱低、中、高剂量组,每组15只。除对照组外,其余各组小鼠背部注射盐酸博莱霉素建立SSc模型,成模后刺山柑总生物碱组小鼠背部外敷刺山柑总生物碱乳膏,青霉胺组给予青霉胺灌胃,对照组、模型组背部外敷不含药基质。末次给药后,Western blot检测皮肤COL1A1表达,ELISA法测定小鼠皮肤Fn和血清AngⅡ、IL-1β水平。结果刺山柑总生物碱中、高剂量可明显降低小鼠皮肤COL1A1表达,刺山柑总生物碱高剂量可降低SSc小鼠皮肤Fn和血清AngⅡ水平(P<0.05),对IL-1β没有明显影响(P>0.05)。结论刺山柑总生物碱可抑制SSc皮肤组织COL1A1和Fn表达,调节AngⅡ的异常升高,改善SSc皮肤纤维化。

Objective To investigate the effect of capparis spinosa total alkaloid on skin fibrosis related indexes of collagen α1 type Ⅰ （COL1A1）,fibronectin （Fn）,angiotensin Ⅱ （Ang Ⅱ） and interleukin-1β （IL-1β） in mice models with systemic sclerosis （SSc）. Methods A total of 90 BALB/c mice were divided into the control group,the model group,the penicillamine group and the capparis spinosa total alkaloid low-,medium- and high-dose group with 15 cases in each group.Mice models with SSc were established by injections of bleomycin in the back except the control group.After modeling,the capparis spinosa total alkaloid groups received external application with capparis spinosa total alkaloid cream,the penicillamine group was given penicillamine for gavage;the control and model group received cream without capparis spinosa total alkaloid.The expression of COL1A1 was detected by Western blot,and the levels of Fn,Ang Ⅱ and IL-1β were measured by ELISA after the last medication. Results The expression of COL1A1 significantly decreased in the capparis spinosa total alkaloid middle- and high-dose groups,the levels of Fn and Ang Ⅱ markedly decreased in the capparis spinosa total alkaloid high-dose group （ P 〈0.05）,but there was no influence on IL-1β （ P 〉 0.05 ）. Conclusion Capparis spinosa total alkaloid can inhibit the expression of COL1A1 and Fn,regulate the abnormal increase of Ang Ⅱ,and improve the skin fibrosis of SSc.