TLR4拮抗剂抑制感染性早产大鼠子宫平滑肌收缩及对MyD88/NF-κB表达的影响

TLR4 antagonist inhibits contraction of uterine smooth muscle in infectious preterm rats and its effect on MyD88/NF-κB channel expression

目的探讨Toll样受体4拮抗剂(TLR4拮抗剂)对感染性早产炎症因子和子宫收缩的保护作用,及其对MyD88/NF-κB通道表达的影响。方法清洁级SD大鼠以2:1的比例雌雄合笼,取雌鼠45只、雄鼠30只,次日清晨发现阴道栓或阴道涂片发现精子为妊娠第0天。随机将孕鼠分为对照组(Control组)、感染性早产模型组(LPS组)和TLR4拮抗剂+LPS组(TLR4组)。HE染色观察子宫组织病理改变,子宫离体肌条检测肌张力变化,ELISA检测血清中炎症因子和氧化应激指标的变化,免疫组化和Western blot检测子宫组织中MyD88/NF-κB通道相关蛋白的表达。结果 TLR4拮抗剂明显改善LPS诱导的大鼠感染性早产子宫组织中炎细胞浸润情况,降低子宫离体肌条肌张力,降低炎症反应和氧化应激,抑制MyD88/NF-κB通道蛋白的表达。结论 TLR4拮抗剂对感染子宫收缩的保护作用可能与MyD88/NF-κB通道相关。

Objective To investigate the protective effect of Toll-like receptor 4 antagonist（TLR4 antagonist） on inflammatory cytokines and uterine contractions in infective premature rats, and its effect on the expression of MyD88/NF-κB pathway. Methods Clean SD rats were male and female in a 2：1 ratio（Forty-five female and 30 male）. The vaginal smears were found early in the morning and the spermatozoa were found on the 0 th day of pregnancy. Pregnant mice were randomly divided into control group, infectious preterm labor model group（LPS group） and TLR4 antagonist ＋ LPS group（TLR4 group）. HE staining was used to observe the pathological changes of the uterus. The changes of muscle tone were detected by ex vivo uterine muscle strips. The changes of inflammatory factors and oxidative stress in serum were measured by ELISA. The expressions of MyD88/NF-κB pathway-related proteins in uterine tissue were detected by immunohistochemistry and Western blot. Results TLR4 antagonists could significantly improve the infiltration of inflammatory cells in uterine tissue, reduce muscle tension of uterine muscle strips, inflammation and oxidative stress, and inhibit the expression of MyD88/NF-κB channel protein. Conclusion The protective effect of TLR4 antagonist on uterine contraction might be related to MyD88/NF-κB pathway in infective premature rats.