咪喹莫特诱导的银屑病样小鼠模型的组织学及免疫学特征初步探究

Histopathologic and immunological features of Imiquimod induced psoriatic mouse model

目的:研究咪喹莫特诱导的银屑病样小鼠模型的皮肤组织学及免疫学特征。方法:将20只BALB/c小鼠随机分为造模组和对照组,每组10只。所有小鼠背部剃毛后,造模组小鼠于背部皮肤及单侧耳部每日涂抹共计62.5 mg的5%咪喹莫特乳膏1次,连续7 d,空白组小鼠涂抹等量凡士林。每日记录小鼠PASI评分及耳部厚度,并于末次涂药24 h后处死,取背部皮肤进行多聚甲醛固定,行HE染色及Ki-67免疫组化分析。取脾脏称重,以流式细胞术检测脾脏中的Th细胞亚群。结果:造模组小鼠于第二天逐渐出现红斑、鳞屑、皮肤增厚及耳部肿胀,其PASI评分随造模时间延长而增加。造模组小鼠皮损出现银屑病样病理改变,其表皮厚度明显增加(t=15.12,P<0.001),且Ki-67阳性率明显上升,每个高倍镜视野下阳性细胞数目明显增加(t=10.50,P<0.001)。造模组小鼠脾脏重量和细胞计数较对照组明显增加,且Th1、Th17细胞亚群的比例及绝对计数较对照组明显上升(P值均<0.05),Th2细胞比例及计数无明显变化(P值均>0.05)。结论:咪喹莫特诱导的银屑病样小鼠模型可较好地模拟寻常型银屑病的临床、组织病理和免疫学特征,是一种有效的银屑病模型。

Objective:To investigate the dermatopathologic and immunological features of Imiquimod induced psoriatic mice model.Methods:Twenty BALB/c mice were grouped in IMQ-model group and control group randomly,each had 10 mice.The IMQ-model mice received a daily topical dose of 62.5 mg of IMQ cream(5%)on the shaved back and left ear for 7 consecutive days.The control group mice were treated similarly with vaseline.The Psoriasis Area and Severity Index score and thickness of left ear were measured daily.The dorsal skin samples were evaluated using H&E section and immunohistochemistry test of Ki-67.The spleens were weighed and the splenocyte were counted.Flow cytometry was used for detection of T-helper-cell subsets.Results:Erythema,scaling,skin thickening and ear swelling appeared on day 2 and deteriorated gradually.The cumulative score kept increasing by day 7.Histologically,the skin of IMQ-model mice showed epidermal proliferation and proinflammatory cells infiltration resembling psoriasis vulgaris.The thickness of epidermis(t=15.12,P<0.001)and expression of Ki-67(t=10.50,P<0.001)were increased in IMQ-model.The weight of spleen and cell-counting of splenocytes increased significantly in IMQ-model group.Compared with control group,the splenic Th1 and Th17 cells showed rise in both proportion and number(all P<0.05),but the Th2 cells did not show significant change(both P>0.05).Conclusion:Imiquimod induced psoriatic mouse model could resemble psoriasis vulgaris closely,which allowed further exploration of psoriasis.