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| 不同剂量瘦素对大鼠机械通气肺损伤的影响 |
| Effect of different doses of leptin on the ventilator-induced lung injury in rats |
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| DOI：10.12089/jca.2019.06.016 |
| 中文关键词: 瘦素 呼吸 机械通气肺损伤 炎症 |
| 英文关键词: Leptin Respiration Ventilator-lnduced lung injury Inflammation |
| 基金项目:青岛市民生科技计划项目(15-9-2-72-nsh) |
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| 中文摘要: |
目的 评价不同剂量瘦素对大鼠机械通气肺损伤的影响。
方法 健康清洁级SD雄性大鼠48只，6～8周龄，采用随机数字表法分为四组：气管切开保留自主呼吸的假手术组（A组）、机械通气模型组（B组）、瘦素10 μg/kg组（C组）和瘦素50 μg/kg组（D组），每组12只。采用10%水合氯醛3.5 ml/kg麻醉大鼠，疼痛反射消失后C组腹腔注射瘦素10 μg/kg，D组腹腔注射瘦素50 μg/kg，A、B组腹腔注射等容量生理盐水，注射后即刻进行气管切开，插管机械通气。A组气管插管后保留自主呼吸，B、C、D组机械通气建立VILI模型，参数设置：VT 20 ml/kg，RR 80次/分，I∶E 1∶1，FiO2 21%，PEEP 0 mmHg，通气时间4 h。分别于基础状态、通气结束时抽取股动脉血进行血气分析。通气结束后放血处死大鼠，在4 ℃下取肺组织并收集支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)，光镜下进行中性粒细胞计数，采用ELISA法测定TNF-α、IL-6、IL-1β浓度；取肺组织称重，计算肺湿干重比(W/D)；观察肺组织病理改变并进行病理评分；采用Western blot检测肺组织研磨液中NF-κB p65含量。
结果 与A组比较，B、C、D组W/D、肺损伤评分、BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织NF-κB p65含量明显升高(P<0.01)。与B组比较，C、D组BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织肺损伤评分、NF-κB p65含量明显降低(P<0.05)。与C组比较，D组BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织肺损伤评分、NF-κB p65含量明显降低(P<0.05)。
结论 瘦素可降低大鼠机械通气肺损伤中炎性因子的表达水平，减轻肺损伤，50 μg/kg较10 μg/kg作用明显。 |
| 英文摘要: |
Ojective To evaluate the effect of leptin on ventilator-induced lung injury (VILI) in rats.
Methods Forty eight pathogen-free adult male SD rats were randomized into four groups averagely: group A (spontaneous breathing), group B (VILI), group C (VILI + Leptin 10 μg/kg intraperitoneally), group D (VILI + leptin 50 μg/kg intraperitoneally). The rats were mechanically ventilated for 4 h with the tidal volume of 20 ml/kg to establish VILI model. Mechanical ventilation parameter settings were as following: the tidal volume was 20 ml/kg, the ventilatory frequency was 80 times/min, I∶E 1∶1, FiO2 was 21%, PEEP was 0 mmHg, time was 4 h. SD rats were anesthetized with intraperitoneal 10% chloral hydrate 3.5 ml/kg, after the pain disappeared, tracheostomized and mechanically ventilated. The control group retained the spontaneous breathing. Leptin was injected intraperitoneally after the rats were anesthetized in groups C and D, while the equal volume of normal saline was given instead in groups A and B. Blood samples were taken from the femoral artery at baseline state and 4 h of MV for detection of PaO2. At the end of mechanical ventilation animals were sacrificed by exsanguination. BALF was collected for neutrophils cell count, TNF-α, IL-6, IL-1β. Lung specimens were obtained for determination of the wet/dry weight ratio (W/D) and examination of pathological changes which were scored. Western blot was used for determine the level of NF-κB p65 in lung tissue.
Results Compared with group A,W/D ratio, examination of pathological changes which were scored and neutrophils cell count, TNF-α, IL-6, IL-1β in BALF and the level of NF-κB p65 in lung tissue were significantly increased in groups B, C and D (P < 0.01). Compared with group B, examination of pathological changes which were scored and neutrophils cell count, TNF-α, IL-6, IL-1β in BALF and the level of NF-κB p65 in lung tissue were significantly decreased in groups C and D (P < 0.05). Compared with group C, examination of pathological changes which were scored and neutrophils cell count, TNF-α, IL-6, IL-1β in BALF and the level of NF-κB p65 in lung tissue were significantly decreased in group D (P < 0.05).
Conclusion Leptin can inhibit the expression of inflammatory factors and reduce inflammatory responses, thus improving ventilator-induced lung injury in rats and high-dose effect is obvious. |
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