基于“温阳达表”探讨麻黄附子细辛汤对SSc模型小鼠皮肤及肺组织纤维化的作用机制

The mechanism of Mahuang FuZi XiXin Decoction on skin and lung tissue fibrosis in SSc model mice based on the"Wen Yang Da Biao"

目的观察麻黄附子细辛汤(MFXT)对SSc模型小鼠皮肤及肺组织中HyP含量,皮肤组织中MMP-1及TIMP-1表达的影响,探讨“温阳达表”法治疗系统性硬化症(systemic sclerosis,SSc)组织纤维化的作用机制。方法将50只雌性BALB/c小鼠随机分为正常组,模型组,麻黄附子细辛汤高、中、低剂量组,每组10只。除正常组外,各组均通过皮下注射博莱霉素(bleomycin,BLM)注射液制备SSc小鼠模型。成模后,麻黄附子细辛汤高、中、低剂量组分别给予麻黄附子细辛汤混悬液9.9,3.3,1.1g/kg,均按0.2ml/10g灌胃容量给药,连续21d。取各组小鼠皮肤及肺组织进行病理形态学观察,ELISA法检测皮肤及肺组织中HyP含量,WB法测定皮肤组织中MMP-1和TIMP-1的表达。结果麻黄附子细辛汤能明显改善SSc小鼠的组织病理变化,显著影响SSc小鼠皮肤及肺组织中HyP含量(P<0.05),调节MMP-1及TIMP-1的表达(P<0.05)。结论麻黄附子细辛汤可下调HyP含量以及调控MMP-1和TIMP-1的平衡,改善SSc模型小鼠皮肤及肺组织纤维化程度,有效治疗SSc组织纤维化,为“温阳达表”法指导治疗SSc组织纤维化提供实验依据。

Objective To observe the effects of Mahuang FuZi XiXin Decoction(MFXT)on the content of HyP,MMP-1 and TIMP-1 expression in skin and lung tissues of SSc model mice,and to explore the mechanism of action of"Wen Yang Da Biao"method in the treatment of SSc tissue fibrosis.Methods Fifty female BALB/c mice were randomly divided into normal group,model group,Mahuang FuZi XiXin decoction high,medium and low dose group(n=10).Except for the normal group,SSc mouse models were prepared by subcutaneous injection of bleomycin(BLM)injection.After molding,Mahuang FuZi XiXin decoction high,medium and low dose groups were given Mahuang FuZi XiXin decoction suspension 9.9g/kg,3.3g/kg,1.1g/kg,all according to 0.2ml/10g gavage capacity for 21 days.The skin and lung tissues of each group of mice were taken for pathological morphological observation,the HyP content in skin and lung tissues was detected by ELISA method,and the expression of MMP-1 and TIMP-1 in skin tissues was measured by WB method.Results Mahuang FuZi XiXin decoction could significantly improve the histopathological changes of SSc mice,significantly affect the HyP content(P<0.05)in the skin and lung tissues of SSc mice,and regulate the expression of MMP-1 and TIMP-1(P<0.05).Conclusion Mahuang FuZi XiXin decoction can downregulate the content of Hyp,regulate the balance of MMP-1 and TIMP-1,improve the degree of skin and lung tissue fibrosis of SSc model mice,and effectively treat SSc tissue fibrosis,which provides an experimental basis for the"Wen Yang Da Biao"method for the treatment of SSc tissue fibrosis.