目的 探讨锰补充对卵清蛋白（ovalbumin,OVA）诱导的肥胖哮喘小鼠肺部炎症的影响,为临床治疗提供新思路。方法 60只雄性昆明小鼠随机分为5组：对照组（CON）、肥胖组（HF）、哮喘组（OVA）、肥胖哮喘组（HF+OVA）、肥胖哮喘锰干预组（Mn,下称Mn干预组）,每组12只。HF组、HF+OVA组、Mn干预组小鼠给予高脂饲料喂养12 w,CON组及OVA组小鼠给予对照饲料喂养12 w。OVA组、HF+OVA组、Mn干预组小鼠在实验的第9、10、11 w的第1日给予0.05 mg/ml OVA致敏液200 μl腹腔注射致敏,第12 w连续3日,每日鼻滴注入0.05 mg/ml的OVA生理盐水溶液50 μl进行激发。Mn干预组在高脂饮食期间每两日一次鼻内给予1 mg/kg MnCl2。最后一次鼻滴暴露后,观察小鼠哮喘行为学改变,检测小鼠气道高反应性。造模期间每2w测量体重,12 w后测量体脂,取材,石蜡切片观察肺组织病理改变,分类计数小鼠支气管肺泡灌洗液中白细胞数量及中性粒细胞比率,检测血清及肺组织锰含量,分析支气管肺泡灌洗液中白细胞介素-6（interleukin-6,IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）水平。结果 与CON组比较,HF组小鼠体重增重12.4%,HF+OVA组小鼠增重23.2%,体脂比分别增加46.1%、67.7%,肥胖模型构建成功。OVA组及HF+OVA组小鼠出现挠鼻、点头呼吸等症状,气道反应性升高,表明哮喘模型建立。小鼠肺组织有明显病理改变,炎症细胞数量增多,IL-6、TNF-α水平升高,且HF+OVA小鼠的症状更明显 (P<0.05)。与HF+OVA组小鼠相比,Mn干预组小鼠体重降低17.9%,体脂比降低27.4%,哮喘症状减轻,气道反应性降低,肺组织病理损伤减轻,炎症细胞数量减少,IL-6、TNF-α水平下降 (P<0.05)。结论 Mn补充对肥胖哮喘小鼠肺部炎症反应有防治作用,其机制可能与抑制炎症反应有关。
Abstract
Objective To explore the effects of manganese supplementation on lung inflammation in obese asthmatic mice exposed to ovalbumin (OVA) and to provide new insights for clinical treatment. Methods Sixty male Kunming mice were randomly divided into five groups: control group (CON), obesity group (HF), asthma group (OVA), obese asthma group (HF+OVA), and obese asthmatic manganese intervention group (Mn, hereinafter referred to as the Mn intervention group), with 12 mice in each group. Groups HF, HF+OVA, and Mn were fed a high-fat diet for 12 weeks, and the other two groups were fed a control diet. Mice in the OVA, HF+OVA, and Mn intervention groups were sensitized by intraperitoneal injection of 200 μl of 0.05 mg/ml OVA sensitization solution on the first day of the 9th, 10th, and 11th weeks. On the 12th week, mice were treated by nasal drip 50 μl of 0.05 mg/ml OVA saline solution for 3 consecutive days to induce asthma. During the feeding period of high-fat diet, the Mn intervention group received 1 mg/kg MnCl2 intranasally every two days to induce asthma. After the last nasal drip exposure, asthmatic behavioral changes were observed and airway hyperresponsiveness was measured. Body weight was measured every fortnight during the modeling period, body composition was measured after 12 weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in lung tissues. White blood cells in mouse bronchoalveolar lavage fluid (BALF) were counted and classified. The Mn contents in the serum and lung tissues were detected, and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF were analyzed. Results Compared with the CON group, the mice in the HF group gained 12.4% in body weight, while the HF+OVA group gained 23.2%. The body fat ratios increased by 46.1% and 67.7% in the HF and HF+OVA groups, indicating the obesity model was successfully constructed. The mice in the OVA and HF+OVA groups showed symptoms such as nose scratching and nodding breathing, with increased airway hyperresponsiveness, indicating that the asthma model was established. Significant pathological changes were observed in the lung tissue of asthma mice, with an increased number of inflammatory cells and elevated levels of IL-6 and TNF-α. These symptoms were more pronounced in HF+OVA mice (P0.05). Compared with the HF+OVA group, mice in the Mn intervention group showed a 17.9% reduction in body weight and a 27.4% reduction in body fat ratio. Meanwhile, asthma symptoms were mitigated, airway hyperresponsiveness decreased, and pathological damages to lung tissues reduced. The number of inflammatory cells was decreased, and the levels of IL-6 and TNF-α levels declined (P0.05). Conclusion Mn supplementation protects against inflammatory responses in the lungs of obese asthmatic mice, and its mechanism is related to inhibited inflammatory responses.
关键词
肥胖 /
哮喘 /
锰 /
炎症反应
Key words
obesity /
asthma /
manganese /
inflammatory response
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基金
辽宁省教育厅基本科研项目（No.jytqn2023437）
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