首页|短链脂肪酸对支气管扩张症模型大鼠的免疫调节作用机制

短链脂肪酸对支气管扩张症模型大鼠的免疫调节作用机制

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[目的]探讨短链脂肪酸(SCFAs)对铜绿假单胞菌(PA)液诱导的支气管扩张症模型大鼠的免疫调节作用机制.[方法]采用随机法将20只SPF级大鼠分为对照组、模型组、SCFAs低剂量组和高剂量组.采用气管注射给予10~128 CFU/mL PA 0.5 mL的方法建立支气管扩张症大鼠模型,SCFAs低、高剂量组大鼠每日分别灌胃给予100、150 mg/kg SCFAs混合液(乙酸、丙酸、丁酸比例为3∶1∶1),对照组和模型组分别灌胃给予生理盐水10 mL/(kg·d),连续7 d.取各组肺组织行HE染色,采用ELISA法检测各组大鼠血清中NF-κB、GM-CSF、IL-17A及IL-22水平,采用Western blot法检测肺组织中STAT3、STAT5及TLR2蛋白表达情况.[结果]模型组大鼠支气管管腔扩张变形,管壁增厚,周围见大量炎性细胞浸润,纤维组织形成;SCFAs低、高剂量组大鼠支气管管腔变形有所恢复,炎性细胞浸润及纤维组织明显减少,且高剂量组改善更为明显.与模型组比较,SCFAs低、高剂量组NF-κB、GM-CSF、IL-17A及IL-22水平显著升高(P<0.05),高剂量组升高更为显著.与模型组比较,低、高剂量组STAT3及TLR2表达水平未见明显改变,STAT5表达水平显著降低(P<0.05),低、高剂量组间差异无统计学意义(P>0.05)[结论]SCFAs可促进炎症因子分泌,在PA诱导的支气管扩张症模型大鼠急性感染期发挥免疫调节作用,其机制认为可能与TLR2/NF-κ B/STAT信号通路有关系.
Mechanism of short chain fatty acids on immunomodulatory effects in rats with bronchiectasis
OBJECTIVE To explore the immunomodulatory mechanism of short chain fatty acids(SCFAs)on the bronchiectasis model rats induced by pseudomonas aeruginosa(PA).METHODS Twenty SPF grade rats were randomly divided into control group,model group,SCFAs low-dose and high-dose groups.The rat model of bronchiectasis was established by endotracheal injection of 0.5 mL of 10-128 CFU/mL PA.The rats in the SCFAs low-dose and high-dose groups were given 100 mg/kg and 150 mg/kg SCFAs mixture(the ratio of acetic acid,propionic acid and butyric acid was 3∶1∶1)daily by intragastric administration,respectively,while the rats in the control group and model group were given 10 mL/(kg·d)normal saline by intragastric administration,for 7 consecutive days.HE staining was performed on lung tissues of each group.The levels of NF-κB,GM-CSF,IL-17A and IL-22 in the serum were detected by ELISA.The expressions of STAT3,STAT5 and TLR2 in lung tissues were detected by Western blot.RESULTS In the model group,the bronchial lumen was dilated and deformed,the tube wall was thickened,a large number of inflammatory cells were infiltrated around the bronchial tube,and fibrous tissues were formed.The bronchial deformation was recovered in the SCFAs low-dose and high-dose groups,the inflammatory cells infiltration and fibrous tissue were significantly reduced,and the improvement was more obvious in the high-dose group.Compared with the model group,the levels of NF-κB,GM-CSF,IL-17A and IL-22 in the SCFAs low-dose and high-dose groups were significantly increased(P<0.05),and the levels in high-dose group were more significant increased.Compared with the model group,the expressions of STAT3 and TLR2 were not significantly changed in the SCFAs low-dose and high-dose groups,while the expression of STAT5 was significantly decreased(P<0.05).There was no statistical significance between low-dose group and high-dose group(P>0.05).CONCLUSIONS SCFAs can promote the secretion of inflammatory factors and play an immunomodulatory role in the acute infection period of PA-induced bronchiectasis model rats,and its mechanism might be related to TLR2/NF-κB/STAT signal pathway.

bronchiectasispseudomonas aeruginosashort chain fatty acidimmunomodulationrats

魏萍、施金晶、翁耀麟

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福建中医药大学第二临床医学院,福建福州 350102

福建中医药大学中西医结合学院,福建福州 350122

支气管扩张症 铜绿假单胞菌 短链脂肪酸 免疫调节 大鼠

福建省卫生健康中青年骨干人才培养项目

2020GGA066

2024

延边大学医学学报
延边大学

延边大学医学学报

影响因子:0.308
ISSN:1000-1824
年,卷(期):2024.47(2)