雷帕霉素对金黄色葡萄球菌诱导的大鼠乳腺炎的保护作用

Protective effect of rapamycin on rats with mastitis induced by Staphylococcus aureus

目的探究雷帕霉素对金黄色葡萄球菌诱导的大鼠乳腺炎的保护作用。方法采用金黄色葡萄球菌感染孕期雌性大鼠建立乳腺炎模型,随机分为模型组、低剂量组、高剂量组,模型组腹腔注射生理盐水,低剂量组、高剂量组腹腔注射不同剂量雷帕霉素,另设空白组腹腔注射生理盐水;检测四组大鼠12、24、48 h乳腺上皮细胞MyD88蛋白的表达水平,乳腺组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、活性氧(ROS)的释放水平。结果经金黄色葡萄球菌感染48 h后,乳腺上皮细胞中MyD88蛋白高于空白组(P<0.05);经过高剂量雷帕霉素处理后,MyD88蛋白降低(P<0.05),48 h接近空白组;建模后12 h乳腺组织中TNF-α和IL-6高于空白组(P<0.05),高剂量组在接菌后24 h、48 h TNF-a和IL-6低于模型组(P<0.05),且低于低剂量组(P<0.05);与空白组比较,低剂量和高剂量组均降低了大鼠乳腺组织中ROS的含量(P<0.05);高剂量组在接菌后24 h和48 h ROS低于低剂量组(P<0.05)。结论雷帕霉素对金黄色葡萄球菌诱导的大鼠乳腺炎具有显著的保护作用,并且高剂量的雷帕霉素效果更显著,呈现一定的剂量依赖性。雷帕霉素主要是通过抑制TLR/MyD88信号通路,降低相关炎症因子IL-6和TNF-a的表达,同时减低ROS的释放水平,最终降低金黄色葡萄球菌感染引起的乳腺组织炎症损伤。

OBJECTIVE To explore the protective effect of rapamycin on rats with mastitis induced by Staphylococcus aureus.METHODS The pregnant rats with S.aureus infection were chosen to establish mastitis models and were randomly divided into the model group,the low-dose group and the high-dose group;the model group was given normal saline injection,the low-dose group was treated with low dose of rapamycin,and the high-dose group was treated with high dose of rapamycin;a blank group was set up and given abdominal injection of normal saline.The expression level of MyD88 in mammary epithelial cells was respectively detected for the four groups of rats after treatment for 12,24 and 48 hours.The release levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and reactive oxygen species(ROS)in mammary tissues were detected.RESULTS After 48 hours,the expression level of MyD88 level in mammary epithelial cells was higher in the three groups of rats treated with S.aureus infection than in the blank group(P<0.05).The MyD88 level declined after the treatment with high dose of rapamycin(P<0.05)and approached to the blank group after 48 hours;the levels of mammary tissue TNF-αand IL-6 of the three groups were significantly higher than those of the blank group after modeling for 12 hours(P<0.05),the levels of TNF-a and IL-6 of the high-dose group were significantly lower than those of the model group after treatment for 24 and 48 hours(P<0.05),the levels of above indexes of the high-dose group were significantly lower than those of the low-dose group(P<0.05).The mammary tissue ROS level of the low-dose group and the high-dose group was significantly lower than that of the blank group(P<0.05);the ROS level of the high-dose group was significantly lower than that of the low-dose group after the treatment for 24 and 48 hours(P<0.05).CONCLUSION Rapamycin shows remarkable protective effect on rats with mastitis induced by S.aureus,the effect of high-dose rapamycin is more remarkable,and it is characterized by certain dose dependence.Rapamycin reduces the S.aureus infection-induced mammary tissue inflammatory damage by inhibiting TLR/MyD88 signaling pathway,reducing the expression levels of inflammatory factors IL-6 and TNF-a as well as the release level of ROS.