Xie Xinran, Zhang Lei, Li Xue, Liu Weihong, Wang Ping, Lin Yan, Han Xuyang, Li Ping
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Beijing Institute of Traditional Chinese Medicine, Beijing, China.
Front Pharmacol. 2021 Mar 3;12:591608. doi: 10.3389/fphar.2021.591608. eCollection 2021.
The pathological mechanism of psoriasis and dyslipidemia comorbidity is unclear, and there are few reports on therapy. By establishing an animal model of ApoE mice induced by imiquimod (IMQ), we explored the effects of Liangxue Jiedu formula (LXJDF), a traditional Chinese herb medicine, on psoriasis and dyslipidemia comorbidity through PI3K/Akt/mTOR pathway. The experiment was divided into a control group, a model group, an LXJDF high-dose group, an LXJDF low-dose group, and a positive drug (atorvastatin) group. Each group of mice was given continuous oral administration once a day. After 3 weeks, the mice dorsal skins were smeared with 62.5 mg of 5% IMQ cream for five consecutive days and continued to be given the corresponding drugs. We observed the effects of LXJDF on skin lesion changes, PASI score, pathological characteristics, blood lipid levels (TC, TG, LDL, HDL, and oxLDL), liver pathology, inflammatory factors in the skin, and the protein expression of PI3K/Akt/mTOR pathway in both the skin and liver. The results showed that LXJDF could significantly improve the psoriasiform skin lesions of IMQ-induced ApoE mice, including the reduction of PASI, thinning of epidermal thickness, inhibition of hyperkeratosis and parakeratosis, and inflammatory infiltration in the dermis, and reduce lipid accumulation in the epidermal. LXJDF could regulate blood lipid levels, reduce liver inflammation, and protect the liver. LXJDF could significantly decrease the gene expressions of inflammatory factors IL-17A, IL-23, IL-6, and TNF-α in the skin. LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions. In conclusion, LXJDF exerts an intervention effect on psoriasis and dyslipidemia comorbidity PI3K/Akt/mTOR and its phosphorylation pathway.
银屑病与血脂异常共病的病理机制尚不清楚,关于其治疗的报道较少。通过建立咪喹莫特(IMQ)诱导的ApoE小鼠动物模型,我们探讨了中药凉血解毒方(LXJDF)通过PI3K/Akt/mTOR通路对银屑病与血脂异常共病的影响。实验分为对照组、模型组、LXJDF高剂量组、LXJDF低剂量组和阳性药物(阿托伐他汀)组。每组小鼠每天连续口服给药1次。3周后,小鼠背部皮肤连续5天涂抹62.5mg的5%IMQ乳膏,并继续给予相应药物。我们观察了LXJDF对皮肤病变变化、银屑病面积和严重程度指数(PASI)评分、病理特征、血脂水平(总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白和氧化低密度脂蛋白)、肝脏病理、皮肤炎症因子以及皮肤和肝脏中PI3K/Akt/mTOR通路蛋白表达的影响。结果表明,LXJDF可显著改善IMQ诱导的ApoE小鼠的银屑病样皮肤病变,包括降低PASI、表皮厚度变薄、抑制角化过度和不全角化以及真皮炎症浸润,并减少表皮脂质蓄积。LXJDF可调节血脂水平,减轻肝脏炎症,保护肝脏。LXJDF可显著降低皮肤中炎症因子IL-17A、IL-23、IL-6和TNF-α的基因表达。LXJDF对PI3K、Akt、mTOR蛋白及其磷酸化表达具有特异性抑制作用。总之,LXJDF通过PI3K/Akt/mTOR及其磷酸化通路对银屑病与血脂异常共病发挥干预作用。