瘦素基因敲除小鼠的银屑病样皮肤炎症程度较轻

Leptin deficiency mitigates cutaneous inflammation in a mouse model of psoriasis

目的探究瘦素对咪喹莫特(IMQ)诱导的银屑病样皮肤炎症的影响。方法选用敲除瘦素基因(ob/ob)的肥胖小鼠与正常对照(wt)小鼠各8只,各分为2组,共4组:ob/ob-IMQ、ob/ob-凡士林、wt-IMQ、wt-凡士林,每组4只。ob/ob-IMQ、wt-IMQ组连续6 d使用IMQ(62.5 mg/背部,10 mg/耳朵)诱导银屑病样皮肤炎症,ob/ob-凡士林、wt-凡士林组涂抹相同剂量凡士林,使用总体征评分(TSS)评估小鼠皮损严重程度,通过HE染色探究造模小鼠的炎症表达。使用流式细胞术检测真皮内树突状细胞、巨噬细胞、中性粒细胞以及表皮内gdT/朗格汉斯细胞等炎症细胞水平,qRT-PCR检测皮损组织中IL-6、IL-17、TNF-α、IL-23等mRNA表达水平。结果与wt-IMQ组小鼠相比,ob/ob-IMQ组小鼠临床症状较轻,耳厚度差较小,TSS评分较低(均P<0.001)。HE染色结果显示,ob/ob-IMQ组小鼠的组织炎症程度较wt-IMQ组低。流式细胞术结果提示,ob/ob-IMQ组表皮内gdT/朗格汉斯细胞的比例明显大于ob/ob-凡士林组(t=2.78,P=0.032);wt-IMQ组真皮内巨噬细胞(t=2.64,P=0.038)和中性粒细胞浸润(t=4.87,P=0.008)明显多于wt-凡士林组;但ob/ob-IMQ组与wt-IMQ组表皮、真皮炎症细胞比例未见明显差异(均P>0.05)。qRT-PCR结果显示,ob/ob-IMQ组小鼠IL-6、IL-17 mRNA相对表达水平低于wt-IMQ组(均P<0.05)。结论瘦素可能在肥胖和银屑病共患病的发病过程中起加重作用。瘦素的缺乏抵消了IMQ诱导的银屑病样皮肤炎症。

Objective To explore the effect of leptin on inflammation in psoriasis-like skin induced by imiquimod(IMQ).Methods Eight leptin gene knockout(ob/ob)obese mice and eight normal control(wt)mice were randomly divided into four groups(n=4 each),i.e.wt-IMQ,wt-vaseline,ob/ob-IMQ,ob/ob-vaseline.Mice were treated with either imiquimod(62.5 mg/back,10 mg/ear)or Vaseline(same dose as imiquimod)for 6 consecutive days.The severity of skin lesions was evaluated with TSS score,and HE staining was used to assess inflammatory cells in the skin.Flow cytometry was used to detect the inflammatory cells in the dermis(dendritic cells,macrophages,neutrophils,etc.)and the epidermis(Langerhans cells,gdT cells),while the expression levels of IL-6,IL-17,TNF-α,IL-23 and other inflammatory factors were detected by qRT-PCR.Results ob/ob-IMQ mice displayed milder clinical symptoms,lesser increases in ear thickness,and lower TSS scores than wt-IMQ mice(all P<0.001).HE staining showed that the extent of cutaneous inflammation was lesser in ob/ob-IMQ mice than in wt-IMQ mice.The proportion of LC and gdT cells in ob/ob-IMQ group was significantly higher than that in ob/ob-vaseline group(t=2.78,P=0.032).The infiltration of dermal macrophages(MFs)(t=2.64,P=0.038)and neutrophils in wt-IMQ group(t=4.87,P=0.008)was more prominent than that in wt-vaseline group.However,there was no significant difference in the proportion of inflammatory cells in the epidermis and the dermis between ob/ob-IMQ and wt-IMQ groups(both P>0.05).Expression levels of inflammatory cytokines(IL-6 and IL-17)in ob/ob-IMQ mice were lower than that in wt-IMQ mice.Conclusions Leptin may aggravate psoriasis in individuals accompanied with obesity.Leptin deficiency counteracts IMQ-induced psoriasis-like cutaneous inflammation.