红花水提液对博来霉素诱导的系统性硬皮症小鼠皮肤和肺纤维化的影响

Effect of safflower water extract on skin and pulmonary fibrosis in bleomycin-induced systemic scleroderma mice

目的观察红花水提液对博来霉素诱导的系统性硬皮症小鼠皮肤和肺纤维化的影响,探讨红花抗纤维化的作用机制。方法将24只BALB/C小鼠随机分为对照组、模型组、红花干预组,每组8只。对照组小鼠皮下注射磷酸盐缓冲液,模型组、红花干预组小鼠皮下注射博来霉素磷酸盐缓冲液,1次/d,三组小鼠均连续皮下注射28 d;与此同时,给予对照组、模型组小鼠生理盐水(0.2 mL/d)灌胃,给予红花干预组小鼠红花水提液(0.2 mL/d,含红花30 mg)灌胃,连续灌胃28 d。比较三组小鼠干预期间的活动度,背部注射区皮肤、脱毛区毛发生长情况,反应度及体质量等;干预结束后第3天处死小鼠,检测比较三组小鼠的皮肤和肺组织病理学变化情况以及肺纤维化程度评分;检测比较三组小鼠肺组织的COLI、α-SMA表达水平;检测比较三组小鼠肺组织COLI-a1、COLI-a2、α-SMA的mRNA表达水平。结果干预期间,红花干预组小鼠的活动度、背部注射区皮肤及脱毛区毛发生长情况、反应度及体质量等一般情况优于模型组小鼠。小鼠皮肤、肺组织HE染色和Masson染色检查结果显示,小鼠肺部组织结构紊乱、炎症细胞浸润及胶原纤维增生情况表现为对照组最轻,红花干预组居中,模型组最严重。模型组、红花干预组小鼠肺纤维化程度评分显著高于对照组,红花干预组小鼠肺纤维化程度评分显著低于模型组,差异有统计学意义(P<0.05)。模型组、红花干预组小鼠肺组织COLI、α-SMA表达水平显著高于对照组,红花干预组小鼠肺组织COLI、α-SMA表达水平显著低于模型组,差异有统计学意义(P<0.05)。模型组小鼠COLI-a1、COLI-a2及α-SMA的mRNA表达水平显著高于对照组;红花干预组小鼠COLI-a1、COLI-a2及α-SMA的mRNA表达水平显著低于模型组,差异有统计学意义(P<0.05)。结论红花水提液对博来霉素诱导的系统性硬皮症小鼠具有很好的抗纤维化作用,这可能与其能显著降低小鼠的COLI、α-SMA表达水平有关。

Objective To observe the effect of safflower water extract on skin and pulmonary fibrosis in bleomycin-induced systemic scleroderma mice,and to explore the anti-fibrosis mechanism of safflower.Methods 24 BALB/C mice were randomly divided into control group,model group and safflower intervention group,with 8 mice in each group.The control group was subcutaneously injected with phosphate buffer,while the model group and safflower intervention group were subcutaneously injected with bleomycin phosphate buffer,once daily.And all three groups of mice received continuous subcutaneous injections for 28 days.At the same time,the control group and the model group were given physiological saline(0.2 mL/d)by intragastric administration,and the safflower intervention group was given safflower water extract(0.2 mL/d,including 30 mg of safflower)by intragastric administration for 28 consecutive days.The activity,hair growth in the skin of injection area on the back and hair removal area,reactivity,and body weight of the three groups during intervention were detected and compared.The mice were sacrificed on the third day after the intervention,and the pathological changes in the skin and lung tissues,as well as the pulmonary fibrosis degree score,were detected and compared among the three groups.The expression levels of COLI andα-SMA in lung tissues of the three groups were detected and compared.The mRNA expression levels of COLI-a1,COLI-a2 andα-SMA in lung tissues of the three groups were detected and compared.Results During intervention,the activity,hair growth in the skin of injection area and hair removal area on the back,reactivity,and body weight of mice in safflower intervention group were better than those in the model group.The results of HE staining and Masson staining of mice skin and lung tissues showed that the lung tissue structure disorder,inflammatory cell infiltration and collagen fiber proliferation in the three groups in a descending order were the model group,the safflower intervention group,the control group.The pulmonary fibrosis degree score in safflower intervention group and model group was significantly higher than that in the control group,which were significantly lower in the safflower intervention group than those in model group,with statistically significant differences(P<0.05).The expression levels of COLI andα-SMA in the lung tissue of mice in the model group and safflower intervention group were significantly higher than those in the control group,which were significantly lower in the safflower intervention group than those in the model group,with statistically significant differences(P<0.05).The mRNA expression levels of COLI-a1,COLI-a2 andα-SMA in model group were significantly higher than those in control group.And the mRNA expression levels mentioned above in the safflower intervention group were significantly lower than those in model group,with statistically significant differences(P<0.05).Conclusion Safflower water extract has a good anti-fibrosis effect on bleomycin-induced systemic scleroderma mice,which may be related to its ability to significantly reduce the expression levels of COLI andα-SMA in mice.