首页|绵羊痒螨重组丝氨酸蛋白酶抑制剂对小鼠银屑病样皮肤炎症的影响

绵羊痒螨重组丝氨酸蛋白酶抑制剂对小鼠银屑病样皮肤炎症的影响

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课题组前期发现绵羊痒螨的重组丝氨酸蛋白酶抑制剂4和5(recombinant serine protease inhibitors 4 and 5,rPsoSP4和rPsoSP5)可体外抑制糜蛋白酶、胰蛋白酶和弹性蛋白酶的活性,因此推测其可能具有抗炎活性,为证实上述推测,评价了 rPsoSP4和rPsoSP5是否可以改善小鼠银屑病样皮肤炎症。BALB/c小鼠随机分为5组,用凡士林或咪喹莫特乳膏(imiquimod cream,IMQ)连续涂抹背部皮肤6 d,建立空白对照组和银屑病模型,期间模型组每日皮内注射 PBS(IMQ 组)或 pET32a(+)载体蛋白(IMQ+pET32a(+)组)或 rPso SP4(IMQ+rPso SP4 组)或rPsoSP5(IMQ+rPsoSP5组),每天观察小鼠银屑病样皮损区变化,于第7天处死小鼠,比较各组皮损组织病理变化和皮损组织中IL-1β、IL-6和TNF-α的转录水平。结果表明:IMQ造模成功,小鼠呈现典型的银屑病样皮损;与模型组(IMQ组)相比,IMQ+rPsoSP4组可有效改善小鼠银屑病样皮损,包括显著抑制小鼠体重减轻(第4~6天,P<0。05,P<0。01,P<0。001)和皮损区红斑(第5~6天)、鳞屑(第4~6天)、皮肤增厚程度(第4~6天)及PASI评分(第3~6天)显著减少(P<0。05,P<0。001)。此外,与IMQ组相比,IMQ+rPsoSP4组皮损区组织病理损伤显著减轻,表皮厚度显著降低(P<0。05),浸润的炎性细胞数量极显著减少(P<0。001),皮损区IL-1β、IL-6和TNF-α mRNA水平极显著降低(P<0。001,P<0。000 1),而IMQ+rPsoSP5组对小鼠银屑病样皮损无明显改善。综上,rPsoSP4可显著改善小鼠银屑病样皮损,具有显著的抗炎活性,而rPsoSP5的抗炎活性不明显。
Effect of Recombinant Serpins of Psoroptes ovis on Psoriasis-like Skin Inflammation in Mice
Our team previously found that recombinant serine protease inhibitors 4 and 5(rPssoSP4 and rPssoSP5)of Psoroptes ovis could inhibit the enzymatic activities of chymotrypsin,trypsin and elastase in vitro,thus we speculated that these two recombinant proteins might have anti-inflammation activities.To confirm the above speculation,we assessed whether rPsoSP4 and rPsoSP5 could improve psoriatic-like skin inflammation in mice.BALB/c mice were random-ly divided into 5 groups(n=6),Vaseline or imiquimod cream(IMQ)was applied daily on the back skin continuously for 6 days to establish the control group and psoriasis model groups.Dur-ing this period,the psoriasis model groups were intradermal injected with PBS(IMQ group)or pET32a(+)-vector protein(IMQ+pET32a(+)group)or rPsoSP4(IMQ+rPsoSP4 group)or rPssoSP5(IMQ+rPssoSP5 group),then the changes of psoriasis-like skin lesions were observed every day,and mice were sacrificed on the 7th day.Subsequently,the pathological changes and the transcription levels of IL-1β,IL-6,and TNF-α in the skin lesions among each group were compared.Results showed that IMQ induced psoriasis-like lesions were successfully established,and the mice appeared typical psoriasis-like lesions.Compared with the model group(IMQ group),IMQ+rPsoSP4 group can effectively attenuated psoriasis-like skin lesions,including significant inhibition of weight loss(from 4th to 6th day,P<0.05,P<0.01,P<0.001)and re-ductions of skin erythema(5th and 6th day),skin scales(from 4th to 6th day),skin thickness(from 4th to 6th day)and PASI score(from 3rd to 6th day)in mice(P<0.05,P<0.001).Additionally,compared with the model group(IMQ group),IMQ+rPsoSP4 group showed that the pathologi-cal damage in the skin lesion was significantly reduced,accompanied by the significant decrease in epidermal thickness(P<0.05)and the number of infiltrated inflammatory cells(P<0.001).Moreover,there was a significantly decreased in mRNA levels of IL-1β,IL-6,and TNF-α in the skin lesion of IMQ+rPsoSP4 group in comparison with IMQ groups,while IMQ+rPsoSP5 group had no significant improvement on psoriatic lesions.In conclusion,rPsoSP4 could signifi-cantly improve psoriasis skin lesion in mice and has significant anti-inflammatory activity,while rPssoSP5 seemed to be no obvious effect.

Psoroptes ovisrPsoSP4rPsoSP5psoriasis-like skin inflammationanti-inflamma-tory activity

田焱、杨富升、李艳娥、梁友萍、樊洁、吴芳燕、古小彬

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四川农业大学动物医学院,成都 611130

绵羊痒螨 rPsoSP4 rPsoSP5 银屑病样皮肤炎症 抗炎活性

2024

畜牧兽医学报
中国畜牧兽医学会

畜牧兽医学报

CSTPCD北大核心
影响因子:0.729
ISSN:0366-6964
年,卷(期):2024.55(12)