Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

Correlation of expression of STAT3,VEGF and differentiation of Th17 cells in psoriasis vulgaris of guinea pig

Objective:To investigate the role of T help 17 cells(Th17)and STAT3-VEGF pathway in pathogenesis of psoriasis.Methods:A total of 50 cases of psoriasis guinea pigs and 20 normal guinea pigs were selected.The ratio of Th17/IL-17 cell in peripheral blood were detected by flow cytometric analysis;STAT3 and VEGF concentrations were measured hy immunohistochemistry and Western blot.Results:The expression of Th17 in peripheral blood were significantly increased in psoriasis[(1.76±0.88)%]compared with controls[(0.48±0.27)%](P<0.05).Th17 related cytokine STAT3 and VEGF were significantly increased in psoriasis compared with controls(P<0.05),and were positively correlated the expression of Th17.Conclusions:The expressions of Th17,STAT3 and VEGF are elevated in psoriasis,which suggests Th17 cells have a potential role in the pathogenesis of psoriasis by STAT3-VEGF pathway.

Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells.Recent studies showed that Signal Transducer and Activator of Transcription 3(STAT3),which plays an important role in cell survival,proliferation,differentiation,angiogenesis,and immune responses,is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions.In addition,STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production,thereby exacerbating the condition of psoriasis.Alantolactone(ALT)is a sesquiterpene lactone compound that could selectively suppress STAT3 activation,but its effectiveness and application in psoriasis treatment have not been determined.In this study,we developed ALT loaded chitosan/hyaluronic acid nanoparticles(CHALT),and investigated its therapeutic potential for psoriasis therapy.CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrialmembrane potential,and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line.In an Imiquimod(IMQ)-induced psoriasis model,the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis.In addition,it was found that CHALT restricted the recruitment of immune cells.These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

Effects of astragalus injection on the skin lesion degree and Caspase-14,SOCS1 and STAT3 levels of psoriasis model in Balb/c nude mice

Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.

银屑病皮损ICAM-3表达的免疫组化研究

用卵白素生物素酶复合物法 ( ABC法 )对 2 0例银屑病患者皮损处的 ICAM- 3表达进行了免疫组化研究。结果表明 :ICAM- 3染色阳性细胞的密度在银屑病皮损部位较非皮损部位以及经局部外用皮质激素治疗后肉眼恢复正常的皮肤部位均有统计学意义的显著增高 ( P<0 .0 0 1)。结果提示银屑病皮损部位 ICAM-

人乳腺癌组织中ICAM-1、LFA-1和VEGFR-3的表达与癌淋巴转移关系的研究

目的观察不同时期,不同转移阶段的人乳腺癌组织中细胞间黏附分子(ICAM-1)和淋巴细胞功能相关抗原1(LFA-1)的表达,探讨ICAM-1和LFA-1对乳腺癌淋巴道转移的影响,为乳腺癌淋巴道转移的分子机制提供理论依据。方法根据不同病变阶段的手术患者切除的乳腺癌标本进行HE染色和免疫组化染色,观察ICAM-1、LFA-1在乳腺癌组织和ICAM-1、LFA-1、VEGFR-3在癌旁组织淋巴管内皮的表达情况。结果随着临床分期的增高和淋巴结转移的发生,ICAM-1和LFA-1在乳腺癌癌细胞和癌巢中的表达阳性率逐渐增高,同时ICAM-1、LFA-1和VEGFR-3在癌旁组织淋巴管内皮细胞的表达阳性率也逐渐增高,具有正相关性,并且ICAM-1和LFA-1在癌旁组织淋巴管内皮细胞的表达之间具有正相关性(P<0.01)。同时发现无论是在乳腺癌癌细胞、癌巢还是在癌旁组织淋巴管内皮细胞,ICAM-1和LFA-1表达的高低都与癌的分化程度、性别、年龄不具有相关性,差异无统计学意义(P>0.05)。结论ICAM-1和LFA-1与乳腺癌的淋巴道转移有关,并且通过两者的协同作用促进了乳腺癌的淋巴道转移。两者在癌组织及癌旁组织淋巴管内皮细胞表达的高低,可以作为数据指标对乳腺癌淋巴道转移的预防和治疗起到一定的指导作用。随着肿瘤的进展,乳腺癌癌旁组织中的淋巴管数量随之增加,可能与乳腺癌的淋巴道转移有关。VEGFR-3在淋巴管内皮细胞的表达具有较高的特异性,可以作为淋巴管内皮细胞的特异性标志物来标志淋巴管。

清毒活血化痰复方颗粒通过ERK1/2/STAT3通路调控脐静脉内皮细胞株ECV304氧糖剥夺/复糖复氧模型ICAM-1表达的实验研究

目的:探讨清毒活血化痰复方颗粒对内皮细胞氧糖剥夺-复糖复氧(OGD/R)模型ERK1/2、STAT3蛋白磷酸化和ICAM-1表达的调控作用。方法:SD大鼠连续5 d灌胃清毒活血化痰复方颗粒(12 g/kg)或等体积生理盐水,制备药物血清和空白血清。脐静脉内皮细胞株ECV304分为正常对照组、氧糖剥夺/复糖复氧模型组、清毒活血化痰复方颗粒药物血清组、清毒活血化痰复方颗粒药物血清+U0126(ERK1/2磷酸化特异性阻断剂)组,分别于复氧复糖后4、24、48、72 h以Western blot检测p-ERK1/2、p-STAT3及ICAM-1蛋白的表达,RT-PCR检测ICAM-1 mRNA的表达。结果:作用24 h清毒活血化痰复方颗粒药物血清可以明显促进ERK1/2的磷酸化,并抑制STAT3磷酸化及ICAM-1的表达,但U0126可以部分阻断清毒活血化痰复方颗粒药物血清的以上作用。结论:清毒活血化痰复方颗粒药物血清可通过ERK1/2/STAT3通路调控OGD/R损伤脐静脉内皮细胞株ECV304 ICAM-1的表达。

异位性皮炎皮损中ICAM-3的表达及临床意义

目的 研究细胞间粘附分子-3(ICAM-3)在异位性皮炎(AD)发病机理中的作用。方法 利用ICAM-3单克隆抗体采用免疫组化SP法检测20例正常皮肤和38例AD皮损中ICAM-3的表达情况，并对其与AD病情及皮损严重程度相关性及与伴有和不伴有呼吸道过敏史的关系进行分析。结果 38例AD均可见真皮内灶状分布的及表皮内散在分布的ICAM-3阳性细胞，20例正常皮肤仅3例见到真皮内散在的和表皮内偶见的阳性细胞，余17例基本不表达ICAM-3；ICAM-3表达随着AD病情及皮损严重而增加，但与是否伴有呼吸道过敏史无关。结论 ICAM-3表达与AD病情及皮损严重程度有一定的关系，在AD的发病机理中起重要作用。

基于STAT-3/NF-κB/ICAM-1通路探讨丹皮酚缓解小鼠结肠炎相关性结直肠癌的作用机制

目的从STAT-3/NF-κB/ICAM-1信号通路探讨丹皮酚缓解小鼠结肠“炎—癌转化”的机制。方法构建结肠“炎—癌转化”小鼠模型,ELISA法检测小鼠血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)和白细胞介素10(interleukin-10,IL-10)水平,Western blot法和免疫组织化学染色法检测小鼠结肠组织内信号转导及转录激活因子3(signal transdncers and activators of transduction-3,STAT-3)、核因子-κB(nuclear factorκB,NF-κB)p65和细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)蛋白表达水平。结果光学显微镜下可见丹皮酚治疗组小鼠结肠的炎症细胞浸润、腺体紊乱等病变明显减轻。丹皮酚可显著降低肿瘤数量、肿瘤质量及脾脏指数(P<0.05),显著降低模型小鼠血清TNF-α、IL-6、IL-1β水平(P<0.05),显著升高血清IL-10水平(P<0.05),显著降低小鼠结肠STAT-3、NF-κB p65和ICAM-1的表达水平(P<0.05),其中以丹皮酚中剂量组的作用为优(P<0.05)。结论丹皮酚能有效缓解小鼠溃疡性结肠炎的炎症反应,其作用机制与调节STAT-3/NF-κB/ICAM-1信号通路有关。

ICAM-1、HPC2及GATA3在宫颈癌中的表达及其临床意义

目的探究细胞间黏附因子-1(ICAM-1)、人多梳蛋白2(HPC2)及GATA结合蛋白3在宫颈癌中的表达及其临床意义。方法选择接受治疗的80例宫颈癌患者为研究组,另选取同期治疗的78例良性宫颈病变为良性病变组,选取80例健康个体为对照组,分别检测其ICAM-1、HPC2及GATA3水平,对比3组个体ICAM-1、HPC2及GATA3水平。将宫颈癌患者按照病理检测结果区分为Ⅰ~Ⅱ期组(36例)与Ⅲ~Ⅳ期组(44例),对比2组患者血清ICAM-1、HPC2及GATA3水平。最后对宫颈癌患者实施为期18个月的随访,对比死亡组(32例)与存活组(48例)患者血清ICAM-1、HPC2及GATA3水平。结果(1)研究组血清ICAM-1、HPC2及GATA3水平高于良性病变组,良性病变组高于对照组,组间对比差异具有统计学意义(P<0.05)。(2)Ⅲ~Ⅳ期组宫颈癌患者血清ICAM-1、HPC2及GATA3水平明显高于Ⅰ~Ⅱ期组(P<0.05)。(3)死亡组宫颈癌患者血清ICAM-1、HPC2及GATA3水平明显高于存活组(P<0.05)。结论ICAM-1、HPC2及GATA3在宫颈癌患者中呈现明显的高表达,同时ICAM-1、HPC2及GATA3水平与宫颈癌患者临床分期及预后有密切的联系。

温热灌流对恶性黑素瘤患者单一核细胞膜LFA-3和ICAM-1表达的动态观察

目的 了解肢体局部温热灌流 (HILP)对恶性黑素瘤 (MM )患者外周血中淋巴细胞和单核细胞膜LFA 3和细胞间粘附分子 1(ICAM 1)表达动态变化的影响。方法 收集经HILP手术MM患者的单一核细胞 ,用抗人LFA 3单抗和抗人ICAM 1单抗进行活细胞双荧光免疫染色 ,经流式细胞计数仪进行检测和统计学分析。结果 LFA 3在手术前表达的淋巴细胞百分数为 5 5 .1% ,平均细胞荧光道数是 4.7meanX ,而在手术后表达则呈上升趋势 ,以手术后第 1天最为明显 ,分别为6 7.4%和 5 .5meanX(P <0 .0 1) ;ICAM 1在手术前表达的淋巴细胞为 45 .5 %和 4.6meanX ,手术 1天后的上升也最为明显 ,分别升为 74.7% (P <0 .0 1)和 4.9meanX。单核细胞膜ICAM 1手术前为 87.0 %和 2 1.3meanX ,手术 1天后上升为 96 .6 %和34 .4meanX(P <0 .0 1)。结论 HILP对增强机体免疫细胞膜ICAM 1和LFA

蒙药珍宝丸对视网膜缺血再灌注损伤中的影响及ICAM-1,Caspase-3的表达

观察ICAM-1,caspase-3在RIR损伤中的表达及蒙药珍宝丸对其的影响并探讨其对RIR损伤中的保护作用。方法:用升高眼压的方法制作兔视网膜缺血模型,在不同时间观察95只家兔视网膜组织病理学改变及ICAM-1,caspase-3的表达。结果:模型组视网膜神经节细胞层,内核层细胞数减少,出现大量的水肿和空泡,内核层细胞排列紊乱。缺血再灌注后6h起改变明显,24h达到高峰72h水肿和空泡减少,视网膜明显变薄。珍宝丸组水肿和空泡现象较模型组轻,内核层和神经节细胞数较模型组多,视网膜较厚,细胞排列有序。ICAM-1,caspase-3的表达6h起明显,24h达到高峰,72h仍少量表达。珍宝丸治疗组各观察指标表达变化规律与缺血再灌注组基本一致,但均较缺血再灌注组明显下降。结论:1.RIR损伤中ICAM-1,caspase-3的表达增高。2.珍宝丸对RIR损伤中ICAM-1,caspase-3的表达有抑制作用。3.珍宝丸对RIR损伤有保护作用。

Analysis of Th1/Th2 Response Pattern for Erythrodermic Psoriasis

As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis（EP） is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells（PBMCs） derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris（PV） patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls（P〈0.05）. Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients（P〈0.01）. The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

宫颈癌组织中Survivin、ICAM-3的表达及与放疗敏感性的关系

目的 探究宫颈癌组织中Survivin、ICAM-3的表达及与放疗敏感性的关系。方法 选取宫颈癌患者50例,根据放疗敏感性的不同将患者分为放疗敏感组(n=28)和放疗抵抗组(n=22)。采用免疫组化分析宫颈癌患者的Survivin、ICAM-3水平,比较其和临床病理特征及放疗敏感性的关系。结果 放疗敏感组和放疗抵抗组的FIGO分期差异无统计学意义(P>0.05),放疗抵抗组肿瘤的分化程度更低,肿瘤直径更大,差异有统计学意义(P<0.05)。放疗敏感组Survivin、ICAM-3的阳性表达率明显低于放疗抵抗组,差异有统计学意义(P<0.05)。多因素分析结果发现,分化程度、肿瘤直径与放疗敏感性无关(P>0.05),Survivin、ICAM-3表达水平与放疗敏感性有关(P<0.05)。结论 宫颈癌患者Survivin、ICAM-3水平以及临床病理特征与放疗敏感性有关,可为今后探索宫颈癌的预后指标提供一定的参考依据。

Fibulin-3、OPN、ICAM-1在腹主动脉瘤中的表达及意义

目的研究腹主动脉瘤患者血清Fibulin-3、骨桥蛋白(OPN)、ICAM-1的表达及意义,分析血清Fibulin-3、OPN、ICAM-1与腹主动脉瘤的关系。方法选取收治的50例腹主动脉瘤患者为AAA组,同时选取同时期体检的50例健康人为对照组。采用酶联免疫吸附法检测Fibulin-3、OPN水平,采用酶标仪双抗体夹心法测定ICAM-1水平。结果AAA组血清Fibulin-3表达水平低于对照组,OPN、ICAM-1表达水平高于对照组,差异有统计学意义(P<0.05)。随着腹主动脉瘤不断增大Fibulin-3表达水平不断降低,OPN、ICAM-1水平表达不断升高(P<0.05)。受试者工作特征(ROC)曲线分析Fibulin-3、OPN、ICAM-1预测腹主动脉瘤的曲线下面积(area under the curve,AUC)分别为0.942、0.616、0.868、0.869。结论Fibulin-3在腹主动脉瘤患者中低表达,OPN、ICAM-1在腹主动脉瘤患者中高表达,Fibulin-3低表达与OPN、ICAM-1高表达是腹主动脉瘤患者发病的风险预测因子。

基于“ICAM-5/ERM/PI3K/AKT信号通路”探讨针刺治疗缺血性中风的作用机制

目的:探究针刺对缺血性中风大鼠梗死灶周围脑组织ICAM-5/ERM/PI3K/AKT信号通路表达的影响。方法:将80只雄性SD大鼠按照区组随机化法,分为正常组、假手术组、模型组和针刺组。正常组常规饲养,不进行干预;假手术组仅予以切开皮肤寻找并剥离神经血管,并不埋入线栓;模型组与针刺组行线栓法制备MCAO模型。造模成功后针刺组大鼠予以针刺治疗,连续针刺治疗两个疗程;假手术组和模型组大鼠仅模仿捉取、归笼的行为。干预结束后对各组大鼠进行神经功能缺损评分;Western blot法检测大鼠脑组织中ICAM-5/ERM/PI3K/AKT的表达水平;TUNEL免疫组化法观察缺血侧大脑组织神经细胞凋亡表达。结果:与正常组比较,假手术组、模型组ICAM-5、ERM、PI3K及AKT蛋白表达水平均有所降低(P<0.05),模型组与假手术组相比,蛋白表达水平下调较为显著(P<0.01);而与模型组相比,针刺组ICAM-5、ERM、PI3K与AKT蛋白表达水平均明显上调,差异具有统计学意义(P<0.05)。模型组、假手术组神经功能评分显著低于正常组(P<0.01或P<0.05),针刺组神经功能评分高于模型组、假手术组(P<0.05)。模型组缺血侧大脑组织有神经细胞坏死征象,且被染色的凋亡细胞显著增加,针刺组与模型组相比变形坏死组织范围较小、程度较轻,被染色的凋亡细胞较之减少。结论:针刺治疗缺血性中风可通过上调ICAM-5、ERM、PI3K及AKT蛋白的表达,激活ICAM-5/ERM/PI3K/AKT信号通路的转导,减轻脑梗死大鼠脑组织炎症反应,改善神经功能。

Galectin-3缺失对银屑病小鼠模型中肥大细胞活化及皮肤损伤的影响

目的:探讨皮肤中半乳糖凝集素-3(Gal3)对银屑病小鼠模型中皮损处肥大细胞激活及银屑病皮炎损伤的影响及其潜在机制。方法:每日分别对SPF级Gal3野生型(Gal3^(+/+))和Gal3基因敲除(Gal3^(−/−))小鼠背部裸露皮肤处涂抹相同剂量咪喹莫特乳膏,连续5 d以构建银屑病小鼠模型。观察小鼠背部大体病变,并根据银屑病皮损面积和严重程度指数(PASI)进行评分,利用实时荧光定量PCR测定小鼠皮损组织细胞因子il-1、il-17表达,比较Gal3^(+/+)小鼠和Gal3^(−/−)小鼠银屑病炎症的严重程度;HE染色观察比较皮损组织病理学变化;甲苯胺蓝染色观察小鼠皮损组织中肥大细胞的形态和分布差异;免疫组织化学和图像分析技术检测肥大细胞活化标志物如类胰蛋白酶和5-羟色胺(5-HT)的表达、分布等差异。结果:连续应用咪喹莫特乳膏后,Gal3^(−/−)小鼠背部出现鳞屑、浸润斑块和红斑等典型银屑病临床表型,而Gal3^(+/+)小鼠背部出现细小鳞屑与少量浸润,Gal3^(−/−)小鼠PASI评分较Gal3^(+/+)小鼠明显升高;Gal3^(+/+)小鼠与Gal3^(−/−)小鼠皮损处il-1、il-17表达升高,但后者炎症因子表达上调更显著。组织病理学观察发现Gal3^(+/+)小鼠表皮稍增厚,Gal3^(−/−)小鼠表皮明显增厚,且网脊向下延伸部分伴有炎症细胞聚集;甲苯胺蓝染色表明Gal3^(+/+)小鼠皮损组织肥大细胞分布稀疏且大部分结构完整,而Gal3^(−/−)小鼠肥大细胞数量增多并广泛分布于皮肤组织,且多数肥大细胞处于活化脱颗粒状态;免疫组织化学染色观察发现Gal3^(−/−)小鼠皮损组织类胰蛋白酶和5-HT较Gal3^(+/+)小鼠表达信号明显增强,且多集中在表皮损伤处。结论:Gal3的缺失引起银屑病小鼠模型皮损处肥大细胞过度活化,加重银屑病皮肤炎症损伤发生和疾病进展,Gal3在该模型中对皮损处肥大细胞活化与脱颗粒有抑制作用。