鼻渊舒口服液对CRS模型小鼠鼻窦黏膜IFN-γ及免疫检查点B7-H1/PD-1mRNA表达的影响研究
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篇名: 鼻渊舒口服液对CRS模型小鼠鼻窦黏膜IFN-γ及免疫检查点B7-H1/PD-1mRNA表达的影响研究
TITLE: Study on the Effects of Biyuanshu Oral Solution on mRNA Expression of IFN-γ and Immune Checkpoint B7-H1/ PD-1 of Nasal Sinus Mucosa in CRS Model Mice
摘要: 目的:探讨鼻渊舒口服液对慢性鼻-鼻窦炎(CRS)模型小鼠γ干扰素(IFN-γ)的影响,并基于协同刺激分子B7同源物l(B7-H1)/程序性死亡因子1(PD-1)免疫检测点探讨其可能机制。方法:将雄性C57小鼠随机分为正常组、假手术组、化学药对照组(克拉霉素,103mg/kg)和鼻渊舒低、中、高剂量组(鼻渊舒口服液,3.1、6.2、12.4mL/kg),每组20只。除正常组不作任何处理外,其余各组小鼠均开放上颌窦,假手术组不填充带菌海绵,模型组和各给药组填充带菌海绵以复制CRS模型。自造模后第8周开始,正常组、假手术组和模型组小鼠均灌胃生理盐水0.2mL,各给药组小鼠灌胃相应药物,每日1次,连续14d。观察小鼠的鼻部症状和一般情况,采用苏木精-伊红染色法观察小鼠鼻窦黏膜的病理变化;采用实时荧光定量聚合酶链式反应法检测小鼠鼻窦黏膜中IFN-γ、B7-H1、PD-1mRNA的表达情况。结果:正常组、假手术组小鼠未见鼻部异常,鼻窦黏膜上皮及纤毛完整,两组IFN-γ、B7-H1、PD-1mRNA的相对表达量比较差异均无统计学意义(P>0.05)。模型组小鼠可见流涕且频繁挠鼻、喷嚏,鼻腔内有少量黄色分泌物,脱毛严重;其鼻窦黏膜严重缺损、纤毛脱落,黏膜下层腺体增生,可见淋巴细胞浸润;鼻窦黏膜中IFN-γ、B7-H1、PD-1mRNA的相对表达量均较正常组显著升高(P<0.01)。与模型组比较,各给药组小鼠的鼻部症状、一般情况及鼻窦组织病理学变化均有不同程度的改善,化学药对照组和鼻渊舒中、高剂量组小鼠鼻窦黏膜中IFN-γ、B7-H1mRNA以及各给药组PD-1mRNA的相对表达量均显著降低,且鼻渊舒中、高剂量上述指标均显著低于低剂量组,而鼻渊舒高剂量组IFN-γmRNA的相对表达量显著高于中剂量组。鼻渊舒低、高剂量组IFN-γmRNA,低剂量组B7-H1mRNA以及各剂量组PD-1mRNA的相对表达量均显著高于化学药对照组(P<0.05或P<0.01);鼻渊舒中剂量组上述指标水平与化学药对照组相当(P>0.05)。结论:鼻渊舒口服液可改善CRS模型小鼠鼻窦黏膜的慢性炎症,其机制可能与通过抑制IFN-γmRNA表达从而干预B7-H1/PD-1mRNA过度表达有关。
ABSTRACT: OBJECTIVE:To investigate the effects of Biyuanshu (BYS)oral solution on IFN-γ of chronic rhinosinusitis (CRS)model mice ,and to investigate its potential mechanism on the basis of B 7-H1/PD-1 immune checkpoint. METHODS :Male C57 mice were randomly divided into normal group ,sham operation group ,chemical medicine control group (clarithromycin,103 mg/kg),BYS low-dose ,medium-dose and high-dose groups (BYS oral solution ,3.1,6.2,12.4 mL/kg),with 20 mice in each group. Except for normal group without any treatment ,other mice were all open maxillary sinus ,sham operation group was not filled with sponge with bacteria ,while model group and administration groups were filled with sponge with bacteria to induce CRS model. Since 8th week after modeling ,normal group ,sham operation group and model group were given normal saline 0.2 mL intragastrically,administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 14 d. The nasal symptoms and general condition of mice were observed ,and the pathological changes of mice ’s nasal sinus mucosa were observed by HE staining ;qRT-PCR was used to measure the mRNA expression of IFN-γ,B7-H1 and PD- 1 in nasal sinus mucosa of mice. RESULTS:The normal group and sham operation group had no abnormal in nose ,and the epithelium and cilia of the nasal sinus mucosa were intact ;there was no significant difference f8y3j0127@163.com in the relative mRNA expression of IFN-γ,B7-H1 and PD- 1 between 2 groups(P>0.05). In model group ,the mice were found to have runny n ose,frequent scratching and sneezing ,a small amount of yellow secretion in the nasal cavity ,and serious depilation ;the nasal sinus mucosa was seriously damaged ,cilia was exfoliated ,and the gland in the submucosa was hyperplasia ,lymphocyte infiltration was also found ;the relative mRNA expression of IFN-γ,B7-H1 and PD- 1 were significantly increased compared with normal group (P<0.01). Compared with model group,the nasal symptoms ,general condition and pathological changes of the nasal sinuses in each administration group were improved in varying degrees ;the relative mRNA expression of IFN-γ and B7-H1 in chemical medicine control group ,BYS medium-dose and high-dose groups ,as well as the relative mRNA expression of PD- 1 in administration groups were decreased significantly;above indexes of BYS medium-dose and high-dose groups were significantly lower than BYS low-dose group ,while relative mRNA expression of IFN-γ in BYS high-dose group were significantly higher than BYS medium-dose group. The relative mRNA expression of IFN-γ in BYS low-dose and medium-dose groups,the relative mRNA expression of B 7-H1 in BYS low-dose group,the relative mRNA expression of PD- 1 in BYS groups were significantly higher than chemical medicine control group ; mRNA expression of IFN-γ in BYS high-dose group was significantly higher than chemical medicine control group(P<0.05 or P< 0.01). Above indexes of BYS medium-dose group were similar to those of chemical medicine control group (P>0.05). CONCLUSIONS:BYS oral solution can improve chronic inflammation in nasal sinus mucosa of mice ,the mechanism of which may be associated with intervening mRNA overexpression of B 7-H1/PD-1 by inhibiting mRNA expression of IFN-γ.
期刊: 2020年第31卷第17期
作者: 付译节,李辉,朱天民,朱鑫,李璐,胡守亮
AUTHORS: FU Yijie,LI Hui,ZHU Tianmin ,ZHU Xin,LI Lu,HU Shouliang
关键字: 鼻渊舒口服液;慢性鼻-鼻窦炎;γ干扰素;协同刺激分子B7同源物l;程序性死亡因子1;免疫检查点;小鼠;机制
KEYWORDS: Biyuanshu oral solution ;Chronic rhinosinusitis ;IFN-γ;B7-H1;PD-1;Immune checkpoint ;Mice;Mechanism
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