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目的探讨凉血解毒利湿方治疗银屑病的可能作用机制。方法 50只BALB/c小鼠随机分为空白对照组、模型组、甲氨蝶呤组及中药高、低剂量组。除空白对照组外,其余各组连续6日外涂5%咪喹莫特乳膏建立银屑病模型,除模型组外,中药高、低剂量组分别给予凉血解毒利湿方42、21 g/(kg·d)灌胃,甲氨蝶呤组给予甲氨蝶呤片1 mg/(kg·d)灌胃,模型组和空白对照组给予0.4 ml蒸馏水,每日1次,共6天。第7天观察小鼠皮损变化情况;HE染色观察皮损组织形态学变化,光镜下测量表皮厚度;免疫荧光法检测小鼠皮损中增殖细胞核抗原(PCNA)有丝分裂细胞核数、有丝分裂细胞率、外皮蛋白、过氧化物酶体增殖激活受体α(PPAR-α)、过氧化物酶体增殖激活受体γ(PPAR-γ)、过氧化物酶体增殖激活受体β/δ(PPAR-β/δ)表达情况;Real-Time PCR、Western blot法分别检测小鼠皮肤中PPAR-α、PPAR-γ、PPAR-β/δmRNA、蛋白表达。结果模型组小鼠皮损鳞屑叠起、红斑色深、浸润较厚;与模型组相比,各给药组皮损症状均有明显改善。与空白对照组比较,模型组小鼠表皮细胞层增厚,有丝分裂细胞核数量均明显增多,有丝分裂细胞率显著升高。与模型组比较,甲氨蝶呤组及中药高、低剂量组PPAR-α、PPAR-γ蛋白表达升高,PPAR-β/δ蛋白表达降低,甲氨蝶呤组PPAR-γ、PPAR-β/δmRNA及中药高、低剂量组PPAR-β/δmRNA均明显降低(P<0.05或P<0.01)。与中药高剂量组比较,中药低剂量组PPAR-β/δmRNA表达降低(P<0.01)。结论凉血解毒利湿方可调控银屑病小鼠皮损中PPARs表达,从而抑制表皮细胞过度增殖和分化,可能是其治疗银屑病的作用机制之一。
Objective To explore the possible mechanism of action of cooling blood and detoxication and dampness on psoriasis. Methods Fifty BALB / c mice were randomly divided into blank control group, model group, methotrexate group and Chinese medicine high and low dose groups. Except for the blank control group, the other groups were given 5% imiquimod cream on the 6th for 6 consecutive days to establish the model of psoriasis. Except for the model group, g / (kg · d) were given intragastrically, methotrexate was given methotrexate 1 mg / (kg · d) orally, the model group and the blank control group were given 0.4 ml of distilled water, 1 times a day, a total of 6 day. The morphological changes of the skin lesions were observed by HE staining and the thickness of the epidermis was measured by light microscopy. The numbers of mitotic nuclei and proliferating cell nuclear antigen (PCNA) (PPAR-α), peroxisome proliferator-activated receptor γ (PPAR-γ), peroxisome proliferator-activated receptor β / δ -β / δ). The expression of PPAR-α, PPAR-γ, PPAR-β / δmRNA and protein in mouse skin were detected by Real-Time PCR and Western blot respectively. Results Compared with the model group, the skin lesions of the mice in the model group were significantly better than those in the model group. Compared with the blank control group, the number of epidermal cell layer in the model group was thicker, the number of mitotic nuclei were significantly increased, and the mitotic cell ratio was significantly increased. Compared with the model group, the expression of PPAR-αand PPAR-γprotein in the methotrexate group and the high-dose and low-dose groups of Chinese herbal medicine increased and the expression of PPAR-β / δprotein decreased. The levels of PPAR-γand PPAR- / δmRNA and PPAR-β / δmRNA in high and low dose groups were significantly decreased (P <0.05 or P <0.01). Compared with the traditional Chinese medicine high-dose group, the expression of PPAR-β / δ mRNA in the low-dose group decreased (P <0.01). Conclusion Liangxue Jiedu dampness can regulate the expression of PPARs in the lesional lesions of psoriatic mice and thus inhibit the excessive proliferation and differentiation of epidermal cells, which may be one of its mechanisms of action in the treatment of psoriasis.