| 苏华振,魏明.氯沙坦对急性肺损伤小鼠肺部组织及肺树突状细胞结构功能的作用[J].安徽医药,2020,24(4):651-655. |
| 氯沙坦对急性肺损伤小鼠肺部组织及肺树突状细胞结构功能的作用 |
| Effects of losartan on lung tissue and structural function of lung dendritic cell in mice with acute lung injury |
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| DOI：10.3969/j.issn.1009?6469.2020.04.004 |
| 中文关键词: 急性肺损伤 树突细胞 呼吸窘迫综合征，成人 氯沙坦 白细胞介素 6 基因， MHCⅡ类 抗原， CD80 |
| 英文关键词: Acute lung injury Dendritic cells Respiratory distress syndrome,adult Losartan Interleukin?6 Genes, MHC class Ⅱ Antigens,CD80 |
| 基金项目: |
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| 中文摘要: |
| 目的探究氯沙坦对急性肺损伤( ALI)小鼠肺部组织及肺树突状细胞( DC)结构功能的作用。方法 2016年 10月至 2018年 12月取 72只 C57BL/6小鼠，按随机数字表法分为健康对照组、 ALI模型组、氯沙坦干预组各 24只。 ALI模型组:向气管中注射 2 mg/kg的脂多糖( LPS)来构建 ALI模型，行气管注射脂多糖的前 30 min，给予腹腔注射等量的磷酸盐缓冲液( PBS)。氯沙坦干预组:在向气管中注射 2 mg/kg脂多糖之前的 30 min，对其进行腹腔中注射 15 mg/kg的氯沙坦。健康对照组:气管中注射 PBS，量与脂多糖是相等的，在行气管中注射 PBS的前 30 min对其进行腹腔 PBS的注射，注射的量与之前相等。在 PBS或脂多糖注射之后的 6、12、24 h使小鼠死亡，收集其肺部组织。肺部结构切片用苏木素 ?伊红( HE)进行染色，光学显微镜下观测肺部结构病理学变化，评估肺部炎症损伤程度，同时检测肺部湿重和体质量的比例( LW/BW)。用酶联免疫吸附法( ELISA)检测肺部结构匀浆中的白细胞介素( IL)?6水平，用流式细胞术检测肺部单个细胞悬浮液中 DC的比重和 CD80、主要组织相容性复合物( MHC)Ⅱ的表达。结果 ALI模型组小鼠的肺部结构中，肺泡间隙加宽，间质内的血管有明显的充血，出血以及炎性细胞的弥漫性浸润现象。经氯沙坦干预的小组小鼠肺部结构受损程度较轻，肺部损伤评分明显减低( P＜0.05)。 ALI模型组小鼠肺部 LW/BW(0.71±0.04)，(0.69±0.05)和( 0.67±0.05)%明显大于健康对照组的同一时间点肺部组织 LW/BW(0.49±0.03)，(0.51±0.04)和(0.50±0.03)%，经氯沙坦干预的小组中 LW/BW(0.63±0.04)(0.61±0.03)和( 0.58±0.06)%与 ALI模型组相比较显著减低，但是仍旧明显大于健康对照组。 ALI模型组的肺部结构中 IL?6(2 864±185)(3 568±369)和( 3 018±264)pg/mg显著大于健康对照组( 396±96)(341±72)和( 355±108)pg/mg，氯沙坦干预组( 2 135±193)39±238)和( 1 786±153)pg/mg能够明显降低 ALI小鼠的肺部结中 IL?6水平( P＜0.05)但是其仍旧显著大于健康对P＜0.05)。 ALI模型组肺 DC比例( 3.18±水平，(25，构，照组(0.43)，(3.34±0.37)和( 3.48±0.45)%显著升高，能够表达 CD80分子的肺 DC(9.78±2.37(10.56±2.69)和( 12.43±3.07)%显著升高( P＜0.05)经氯沙坦干预过的小鼠表达 CD80分子的肺部 DC与 ALI模型组相比较降低，但其仍旧明显大于健康对照组(P＜0.05)。氯沙坦干预以及 ALI模型组两部分表达的 MHC Ⅱ的 DC比较，差异无统计学意义( P＞0.05)。结论 氯沙坦能够对 ALI产生局部的保护效果，提示其对 ALI发挥抗炎和免疫调控作用可能是通过对肺 DC的成熟抑制来实现的。 |
| 英文摘要: |
| Objective To assess the effects of Losartan on lung tissue and structural function of lung dendritic cell(DC)in mice with acute lung injury(ALI).Methods From October 2016 to December 2018 72 C57BL/6 mice were randomly assigned into con? trol group(n＝24)，ALI model group(n＝24)and losartan intervention group(n＝24).The mice in ALI model group received 2 mg/kg of lipopolysaccharide(LPS)to establish an ALI model，30 minutes before which an intraperitoneal injection of 2 mg/kg of phosphate buffered saline(PBS)was given.The mice in losartan intervention group received 2 mg/kg of LPS，30 minutes before which an intraperitoneal injection of 15 mg/kg of losartan was given.The mice in control group received 2 mg/kg of PBS，30 min? utes before which an intraperitoneal injection of 2 mg/kg of PBS was given.The mice were put to death 6，12，24h after the injectionof PBS or LPS and the lung tissues were collected.Pulmonary structural slices were stained with hematoxylin?eosin(HE)，and path?ological changes in lung structure were observed under the optical microscope to assess the inflammatory damage in the lungs.Meanwhile，lung wet weight/body weight ratio(LW/BW)was detected.Enzymatic immunoadsorption(ELISA)was used to detect the level of leukocyte interleukin(IL)?6 in lung structural homogenate，and flow cytometry was used to detect DC’s proportion and the expressions of CD80 and major histocompatibility complex(MHC)Ⅱ in a single cell suspension in the lungs.Results Histologi?cally，the interstitium of pulmonary alveoli widened，and significant congestion，hemorrhage and diffuse infiltration of inflammatory cells could be found in the blood vessels through the interstitium.Whereas，the damage to lung structure in mice of losartan inter? vention group was less and the lung damage score was significantly reduced(P＜0.05)..LW/BW of the mice in ALI group was sig? nificantly higher than that of the control group at the same time point(0.71±0.04，0.69±0.05 and 0.67±0.05)% vs.(0.49±0.03，0.51±0.04 and 0.50±0.03)%.LW/BW of the mice in losartan intervention group was significantly lower than that of the ALI model group，but still significantly higher than that of the control group(0.63±0.04，0.61±0.03 and 0.58±0.06)%.Meanwhile，the levels of IL?6 in lung tissues of ALI model group were significantly higher that those of the control group(2864±185，3568±369 and 3018± 264)pg/mg vs.(396±96，341±72 and 355±108)pg/mg.The levels of IL?6 in lung tissues of losartan intervention group was signifi? cantly decreased(2135±193，2539±238 and 1786±153)pg/mg，but still significantly higher than those of the control group(P＜0.05).DC’s proportion in ALI model group(3.18±0.43，3.34±0.37 and 3.48±0.45)% increased significantly，DC’s proportion ex? pressing CD80 molecules(9.78±2.37，10.56±2.69和 12.43±3.07)% increased significantly(P＜0.05).DC’s proportion of the mice in losartan intervention group was significantly decreased in comparison with that in ALI model group，but still significantly higher than that in control group(P＜0.05).There was no significant difference in the expression of MHCⅡ between losartan intervention group and ALI model group(P＜0.05).Conclusions Losartan may produce partial protection to ALI，whose anti?inflammatory and immune regulatory effects may be realized by inhibiting the activation of pulmonary DC. |
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