辛伐他汀对小鼠巨细胞病毒肺炎Toll样受体2表达的影响

发布时间：2018-02-01 07:11

本文关键词： 辛伐他汀巨细胞病毒 Toll样受体干扰素γ 单核细胞趋化蛋白　出处：《中国病理生理杂志》2017年10期 　论文类型：期刊论文

【摘要】：目的:观察辛伐他汀对小鼠巨细胞病毒(MCMV)肺炎小鼠肺组织Toll样受体2(Toll-like receptor2,TLR-2)、干扰素γ(IFN-γ)和单核细胞趋化蛋白1(MCP-1)表达的影响,并探讨辛伐他汀干预MCMV肺炎的可能机制。方法:将40只6~8周龄BALB/c小鼠随机分成5组:正常对照(NC)组、MCMV感染组和辛伐他汀干预(SMV1、SMV2和SMV3)组。SMV1、SMV2和SMV3组分别在腹腔注射MCMV前7 d、与MCMV同时和MCMV感染后3 d给予辛伐他汀(50 mg·kg~(-1)·d~(-1),均连续给药7 d)灌胃,NC组及MCMV组分别予以同体积的生理盐水灌胃。HE染色观察小鼠肺组织的病理改变,real-time PCR检测MCMV DNA的变化,免疫组化和Western blot检测肺组织中TLR-2的表达,ELISA检测肺组织中IFN-γ和MCP-1的变化。结果:与NC组相比,MCMV组肺组织病理染色显示肺泡间质水肿,肺泡壁增宽,内可见大量炎性细胞浸润;肺组织中TLR-2的表达增加,MCMV DNA含量升高,肺组织中炎症因子IFN-γ和MCP-1明显增多(P0.05)。辛伐他汀干预后,与MCMV组相比,肺组织病理改变较前减轻,TLR-2的表达下降(P0.05),MCMV DNA含量降低(P0.05),炎性因子IFN-γ和MCP-1明显下降(P0.05),且SMV1组TLR-2的表达量及MCMV DNA含量下降较SMV2和SMV3组更明显(P0.05),而SMV2和SMV3两组相比差异无统计学显著性。结论:辛伐他汀干预通过下调TLR-2信号通路而降低TLR-2的表达,减少IFN-γ和MCP-1的分泌,并抑制MCMV DNA的复制,从而使肺组织的病理损害得以减轻;且提前给予辛伐他汀干预对预防MCMV的感染及减轻炎症反应具有重要作用。
[Abstract]:Objective: to observe the effect of simvastatin on Toll like receptor 2 (Toll-like receptor 2) and TLR-2 (TLR-2) in lung tissue of mice with cytomegalovirus (CMV) pneumonia. Interferon 纬 (IFN- 纬) and monocyte chemoattractant protein 1 (MCP-1). Methods: forty 6-week old BALB/c mice were randomly divided into 5 groups: normal control group. MCMV infection group and simvastatin intervention group (SMV1 + SMV2 and SMV3) group. SMV1 + SMV2 and SMV3 groups were injected MCMV 7 days before intraperitoneal injection. Simvastatin 50 mg 路kg-1) 路dan-1 was given to MCMV and MCMV 3 days after infection, and they were given intragastric administration for 7 days in a continuous dose of 5 mg 路kg ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路d ~ (-1). The pathological changes of lung tissue in NC group and MCMV group were observed by intragastric perfusion of normal saline in the same volume. The changes of MCMV DNA were detected by real-time PCR. Immunohistochemistry and Western blot were used to detect the expression of TLR-2 in lung tissue. Results: compared with NC group, the changes of IFN- 纬 and MCP-1 in lung tissue were detected by Elisa. In MCMV group, the alveolar interstitial edema was observed by pathological staining, the alveolar wall widened, and a large number of inflammatory cells were found in the alveolar wall. The expression of TLR-2 in lung tissue increased and the content of MCMV DNA increased, and the inflammatory factors IFN- 纬 and MCP-1 increased significantly. Compared with MCMV group, the pathological changes of lung tissue reduced the expression of TLR-2 and the content of MCMV DNA decreased (P0.05). The inflammatory factor IFN- 纬 and MCP-1 decreased significantly (P0.05). The expression of TLR-2 and the content of MCMV DNA in SMV1 group were significantly lower than those in SMV2 and SMV3 group (P 0.05). There was no significant difference between SMV2 and SMV3. Conclusion: simvastatin can decrease the expression of TLR-2 by down-regulating TLR-2 signaling pathway. The secretion of IFN- 纬 and MCP-1 was reduced, and the replication of MCMV DNA was inhibited, so that the pathological damage of lung tissue was alleviated. Early administration of simvastatin plays an important role in preventing MCMV infection and alleviating inflammation.
【作者单位】：徐州市中心医院呼吸内科;徐州医科大学附属医院呼吸内科;
【基金】：江苏省六大人才高峰项目(No.2014-WSN-043)
【分类号】：R563.1
【正文快照】： 巨细胞病毒(cytomegalovirus,CMV)是一种普遍存在的双链DNA病毒,其通常呈隐性感染,多数感染者无临床症状,但在一定条件下可以侵袭多个器官和系统产生严重疾病。数十年来,预防CMV感染的药物不仅有限,而且结果往往不能令人满意,因此,迫切需要一种新的更加安全有效的药物以预防CM

【相似文献】