NLRP3炎症小体激活在急性大鼠乳腺炎中的作用

Role of inflammasome NLRP3 activation in acute rat mastitis

为探讨炎症小体NLRP3在大肠杆菌诱发的实验性大鼠乳腺炎中的作用,36只SD大鼠随机分为对照组、大肠杆菌组和抑制剂组。其中:大肠杆菌组于大鼠产后72 h经乳头管注入2×10^(12) CFU/mL大肠杆菌悬液100μL/侧到第4对乳腺(两侧)内;抑制剂组在注射大肠杆菌悬液前0.5 h腹腔注射500 mg/kg格列本脲;对照组注射等量灭菌生理盐水,注射后12 h收集血清及乳腺组织。结果:大肠杆菌诱发能显著提高乳腺组织NLRP3及衔接蛋白ASC和炎症相关蛋白激酶Caspase-1的表达,促进炎性细胞因子IL-1β的释放,从而引起N-乙酰-β-D-氨基葡萄糖苷酶(NAGase)活性及丙二醛(MDA)水平的显著升高。NLRP3的抑制剂格列本脲预处理能抑制NLRP3及ASC和Caspase-1的表达,降低炎性细胞因子IL-1β的释放,下调NAGase的活性和MDA水平。可见NLRP3炎症小体的激活在大肠杆菌诱导的实验性乳腺炎症反应中发挥了重要的作用。

In order to investigate the role of NLRP3 inflammasome in rats with experimental mastitis induced by Escherichia coli,thirty-six pregnant SD rats were randomly divided into three groups:the control group,the E.coli treatment group and the inhibitor group.E.coli(2×10^(12) CFU/mL)was infused into the mammary gland 72 h after parturition to establish a model of mastitis.The inhibitor groups were given 500 mg/kg glibenclamide(the inhibitor of NLRP3)30 minutes before E.coli injection.12 h after the infusion,rats from each group were euthanized;and mammary gland tissue and serum samples were collected from the rodents.The results showed that the expression of NLRP3,ASC and Caspase-1 was significantly increased,compared with the control group after E.coli infusion,the secretion of IL-1βand MDA and the activity of NAGase were also significantly increased.Compared with the E.coli model group,the NLRP3 inhibitor significantly reduced the expression of NLRP3,ASC and Caspase-1,and thus significantly decreased the secretion of IL-1βand MDA and the activity of NAGase.These findings suggest that the activation of NLRP3 inflammasome plays an important role in E.coli induced experimental breast inflammation.