丁酸钠对老年和青年小鼠哮喘作用的效果比较  

Effects of sodium butyrate on asthma in aged and young mice

作　　者：李晗宇 王安鸽 李姝敏 张勤[1,2] Li Hanyu;Wang Ange;Li Shumin;Zhang Qin(Department of Geriatrics,the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310000;Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physical-Chemical Injury Diseases,the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310000)

机构地区：[1]浙江大学医学院附属第一医院老年医学科 [2]浙江省增龄与理化损伤性疾病诊治研究重点实验室,3100001

出　　处：《中华老年医学杂志》2022年第11期1365-1370,共6页Chinese Journal of Geriatrics

基　　金：浙江省医药卫生科技计划项目,创新人才支持计划项目(2020387174)。

摘　　要：目的比较丁酸钠对老年与青年哮喘小鼠作用的效果。方法分别将24月龄(18只)和4月龄(18只)雄性C57BL/6小鼠,用随机数字法分为3组,对照组(Ctrl),模型组(OVA),处理组(OVA+Sob),每组各6只。OVA抗原激发前2 d,处理组给予腹腔注射1 mg/g丁酸钠(Sob),OVA组和Ctrl组给予生理盐水干预,末次激发后1 d进行终点评估。比较不同月龄小鼠Ctrl组、OVA组和OVA+Sob组之间的气道高反应性(AHR)、肺组织切片苏木精-伊红(HE)病理表现以及肺组织炎症因子的差异,评价Sob对不同月龄哮喘小鼠的作用。结果乙酰甲胆碱(Mch)6.250 g/L(276.28±113.62和103.02±19.55,t=3.368,P=0.026)、12.500 g/L(457.53±157.29和114.76±20.28,t=4.338,P=0.022)、25.000 g/L(1113.16±256.98和567.87±187.34,t=3.538,P=0.009)刺激下,老年OVA组AHR较青年OVA组升高;HE染色显示,老年Ctrl组与青年Ctrl组比较,肺泡腔面积减少,部分实性变,肺间质纤维结缔组织增生,肺泡上皮细胞,毛细血管内皮细胞增生;与各自Ctrl组比较,老年OVA组显著升高的细胞因子为嗜酸性粒细胞趋化因子(Eotaxin)(P=0.035)、IL(白细胞介素)-17A(P=0.004)和IL-1β(P=0.001)。青年OVA组中升高的细胞因子为Eotaxin(P=0.001)、IL-17A(P=0.001)、IL-4(P=0.004)、角质形成细胞的趋化因子(KC)(P=0.012)和IL-1β(P<0.001);青年OVA组与老年OVA组比较,IL-4升高(Z=2.882,P=0.004);IL-1β降低(t=2.728,P=0.020);观察Sob对不同月龄哮喘小鼠的作用效果,Mch 12.500 g/L(P=0.015)、25.000 g/L(P=0.014)刺激下,老年OVA+Sob组AHR较老年OVA组缓解;Mch 3.125 g/L刺激时,青年OVA+Sob组AHR较青年OVA组下降(P=0.021);与青年OVA组比较,青年OVA+Sob组中IL-4(P=0.004)和IL-1β(P=0.014)降低。结论老年小鼠哮喘程度较青年小鼠更严重,可能与不同免疫表型相关;Sob对青年哮喘小鼠炎症因子的缓解作用,可能与青年哮喘小鼠AHR严重程度较老年小鼠轻有关。Objective To compare the effects of sodium butyrate(Sob)on aged and young asthmatic mice.Methods Male C57BL/6 mice aged 24 months(n=18)and 4 months(n=18)were divided using randomly generated numbers into 3 groups:a control group,a model group(treated with ovalbumin,OVA),and a treatment group(OVA+Sob),with 6 mice in each group.The control group was given normal saline as the blank control.Two days before the OVA challenge,the treatment group was given 1 mg/g Sob by intraperitoneal injections and the OVA+Sob group and the control group were given normal saline intervention.Endpoint evaluation was performed 1 day after the last challenge.Differences in airway hyperresponsiveness(AHR),pathological manifestations of lung tissue sections stained with hematoxylin eosin(HE),and inflammatory factors in lung tissues were compared between aged and young mice and the effects of Sob on asthmatic mice of different ages were evaluated.Results Under the stimulation of methacholine(Mch),AHR of the O-OVA group was significantly higher than that of the Y-OVA group(6.250 g/L:276.28±113.62 vs.103.02±19.55,t=3.368,P=0.026;12.500 g/L:457.5±157.29 vs.114.76±20.28,t=4.338,P=0.022;25.000 g/L:1113.16±256.98 vs.567.87±187.34,t=3.538,P=0.009).HE staining revealed that,compared with the Y-control group,the O-control group exhibited a reduced area of alveolar cavity,partial lung consolidation,proliferation of interstitial fibrous connective tissues,alveolar epithelial cells and capillary endothelial cells.Compared with its control group,the O-OVA group had significantly elevated levels of eotaxin(P=0.035),IL-17A(P=0.004)and IL-1β(P=0.001),among the inflammatory factors,whereas the Y-OVA group had elevated levels of eotaxin(P=0.001),IL-17A(P=0.001),IL-4(P=0.004),KC(P=0.012)and IL-1β(P<0.001).Compared with the O-OVA group,the Y-OVA group had increased levels of IL-4(Z=2.882,P=0.004)but decreased levels of IL-1β(t=2.728,P=0.020).As for the effects of Sob on asthmatic mice of different ages,AHR of the O-OVA+Sob group was significantly all

关 键 词：哮喘 羟丁酸钠 脂肪酸类 

分 类 号：R562.25[医药卫生—呼吸系统]