目的 探讨在咪喹莫特(IMQ)诱导的银屑病样小鼠模型中再次诱导是否可以模拟复发表型及组织常驻记忆性T细胞(TRM)的变化.方法 将20只C57BL/6小鼠编号后随机等分为两组,每组10只.所有小鼠背部剃毛后,一组小鼠涂抹62.5 mg凡士林(vaseline),另一组小鼠涂抹62.5 mg的5％咪喹莫特乳膏,连续6 d.第6天处死每组小鼠中的5只小鼠(Vaseline组和IMQ组),第36天时两组剩余小鼠背部皮肤均再次涂62.5 mg咪喹莫特(Vaseline-IMQ组和IMQ-IMQ组),连续6 d后处死小鼠.每日记录小鼠背部皮损严重程度指数(PASI),取背部皮肤进行HE染色.取脾脏及皮肤获取单细胞悬液,进行流式细胞检测.结果 在第6天处死时,IMQ组银屑病样皮损典型,PASI评分最高为(9.50±0.58).在第42天处死时,再次诱导的IMQ-IMQ组PASI评分为(10.75±0.50),比单次诱导的IMQ 组(P = 0.03)和 Vaseline-IMQ 组(8.25±1.50,P＜0.0001)PASI 评分高,且比单次诱导的银屑病样皮损出现更快且更重.IMQ-IMQ组病理切片表皮厚度为(85.68±32.83)μm,比 IMQ 组(59.34±19.33)μm 和 Vaseline-IMQ 组(52.04±11.94)μm更厚,差异均有统计学意义(P＜0.000 1).IMQ-IMQ组脾脏Th17细胞比例增高为(5.17±1.94)％,高于 IMQ 组(3.36±0.58)％(P = 0.18)和 Vaseline-IMQ 组(1.87±1.69)％(P=0.006).IMQ-IMQ 组小鼠背部皮肤的 CD8+CD103+TRM比例为(5.29±2.25)％,显著高于IMQ 组(0.63±0.18)％(P= 0.000 1)和Vaseline-IMQ组(1.12±0.61)％(P= 0.000 4).结论 咪喹莫特诱导的银屑病样小鼠模型在间隔1个月后再次诱导,银屑病样皮损更重、反应更快、表皮增厚更多,且存在更多的Th17细胞和CD8+CD103+TRM,有可能作为银屑病研究中的小鼠复发模型.

Objective:To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (MSCs) on psoriasis-like mouse models induced by imiquimod and the underlying mechanisms.Methods:Eighteen C57BL/6 mice were randomly and equally divided into vaseline group, model group and treatment group according to a random number table. The mice in the model group and treatment group received topical treatment with 5% imiquimod cream at a dose of 62.5 mg once a day for 6 consecutive days on the shaved back, and those in the vaseline group received the treatment with the same amount of vaseline ointment; the mice in the treatment group were injected with 1.5×10 6 human umbilical cord MSCs via the caudal vein on days 1 and 4. The severity of skin lesions on the back of the mice was assessed everyday according to the psoriasis area and severity index (PASI) . Twenty-four hours after the last treatment, that is, on day 7, blood samples were taken, and the mice were sacrificed. The dorsal skin tissues were resected and subjected to hematoxylin and eosin (HE) staining. A single cell suspension of the resected spleen was prepared, and flow cytometry was performed to detect the Th1 and Th17 cell subsets in the spleen cells. Enzyme-linked immunosorbent assay was conducted to detect serum levels of cytokines interleukin (IL) -17A and tumor necrosis factor (TNF) -α. One-way analysis of variance was used for comparisons among groups, Tukey test for multiple comparisons, and repeated measures analysis of variance for the analysis of changes in the PASI score over time. Results:On day 7, there was obvious scaly erythema on the back of the mice in the model group, and the skin thickness and number of infiltrating inflammatory cells were significantly higher in the model group (78.73 ± 23.11 μm, 36.16 ± 2.95 cells/mm 2) than in the vaseline group (13.28 ± 4.57 μm, 13.33 ± 1.15 cells/mm 2, q=19.25, 7.21, respectively, both P < 0.001) . The treatment group showed significantly decreased PASI score, epidermal thickness and number of infiltrating inflammatory cells compared with the model group (all P < 0.001) . The percentage of Th17 cell subsets in the spleen cells and serum level of TNF-α were significantly lower in the treatment group than in the model group (both P < 0.05) . There were no significant differences in the spleen weight, spleen index, spleen cell count, Th1 cell percentage or serum IL-17A level between the treatment group and the model group (all P>0.05) . Conclusion:Human umbilical cord MSCs can effectively alleviate skin inflammation induced by imiquimod in the psoriasis-like mouse models, likely by inhibiting Th17 cell formation and TNF-α expression.

Objective To observe the level of serum beta2-microglobulin (β2-MG) in hemodialysis patients with chronic hepatitis B, and to discuss its influencing factors. Methods Referring to Guidelines for Chronic Hepatitis B in China (version 2010), 30 hemodialysis patients with chronic hepatitis B were included in this study. And 30 hemodialysis patients without hepatitis B virus (HBV) were selected as controls. Blood laboratory indexes were compared by test. Factors influnecing serum β2-MG were analyzed with multiple linear regres-sion analysis. Results The level of serum β2-MG in the HBV-positive group was (65.64±10.18) μg/ml which was significantly higher than (44.90±12.81) μg/ml in the HBV-negative group ( <0.01). Multiple linear regression analyses showed that the level of serum β2-MG was negatively correlated to serum albumin (ALB) (B= -0.001, = 0.015), and positively correlated to HBV infection, duration of dialysis and alanine amino-transferase (ALT) (B=14.127, 0.421 and 0.077; =0.000, 0.001 and 0.032 respectively). Conclusions The level of serum β2-MG in hemodialysis patients with chronic hepatitis B is significantly high when compared with hemodialysis patients without HBV infection. And serum β2-MG is associated with serum ALB and ALT,HBV infection and duration of dialysis.