中国中西医结合急救杂志
中國中西醫結閤急救雜誌
중국중서의결합급구잡지
INTEGRATED TRADITIONAL CHINESE AND WESTERN MEDICINE IN PRACTICE OF CRITICAL CARE MEDICINE
2014年
3期
170-174
,共5页
马明明%李岩%朱委委%张小强%李君%刘向勇%王晓芝
馬明明%李巖%硃委委%張小彊%李君%劉嚮勇%王曉芝
마명명%리암%주위위%장소강%리군%류향용%왕효지
芹菜素%脂多糖%急性肺损伤%肿瘤坏死因子-α%细胞间黏附分子-1%p38丝裂素活化蛋白激酶
芹菜素%脂多糖%急性肺損傷%腫瘤壞死因子-α%細胞間黏附分子-1%p38絲裂素活化蛋白激酶
근채소%지다당%급성폐손상%종류배사인자-α%세포간점부분자-1%p38사렬소활화단백격매
Apigenin%Lipopolysaccharide%Acute lung injury%Tumor necrosis factor-α%Intercellular adhesion molecule-1%p38 mitogen-activated protein kinase signaling pathway
目的：观察芹菜素对脂多糖（LPS）诱导小鼠急性肺损伤（ALI）的影响，探讨其可能的作用机制。方法将40只健康雄性昆明小鼠按随机数字表法分为对照组、模型组及芹菜素低、中、高剂量组，每组8只。采用腹腔注射LPS 5 mg/kg制备ALI模型；芹菜素低、中、高剂量组分别于制模前1 h腹腔注射芹菜素10、25、50 mg/kg进行干预。制模后6 h进行指标检测，取右肺上叶行苏木素-伊红（HE）染色观察肺组织病理改变并对其进行病理评分，取右肺下叶称重测湿/干质量（W/D）比值，酶联免疫吸附试验（ELISA）检测血清及支气管肺泡灌洗液（BALF）中细胞间黏附分子-1（ICAM-1）和肿瘤坏死因子-α（TNF-α）的含量，逆转录-聚合酶链反应（RT-PCR）检测p38丝裂素活化蛋白激酶（p38MAPK）、ICAM-1和TNF-α的mRNA表达。结果与对照组比较，模型组肺W/D比值增高（17.79±2.89比5.56±0.37，P＜0.05），肺组织病理评分增加（分：10.32±0.23比1.87±0.54，P＜0.05），血清及BALF中ICAM-1、TNF-α含量升高〔血清中ICAM-1（ng/L）：21.4±2.7比14.3±3.5，TNF-α（ng/L）：254.8±10.6比142.3±13.7；BALF 中 ICAM-1（ng/L）：20.3±2.4比11.5±3.2，TNF-α（ng/L）：230.3±5.8比110.5±11.2，均 P＜0.05〕，且 p38MAPK、ICAM-1和 TNF-α的mRNA表达亦明显升高（以对照组为1，p38MAPK、ICAM-1、TNF-α的相对表达量分别为4.42±0.37、4.89±0.27、3.28±0.13，均P＜0.05）；不同剂量芹菜素可减轻上述损伤效应，以中剂量组改善最为明显，肺W/D比值为13.28±1.21，血清中ICAM-1为（18.5±4.3）ng/L，TNF-α为（169.4±20.8）ng/L，BALF中ICAM-1为（17.8±3.5）ng/L，TNF-α为（150.4±7.1）ng/L，肺组织p38MAPK、ICAM-1、TNF-α的mRNA表达分别为2.99±0.28、3.97±0.17、2.87±0.27，与模型组比较差异均有统计学意义（P＜0.05或P＜0.01）。结论芹菜素可不同程度的拮抗LPS引起的小鼠ALI，以中剂量组改善效果最好，其保护作用可能与抑制p38MAPK信号通路活化、减少TNF-α和ICAM-1等炎症因子表达有关。
目的：觀察芹菜素對脂多糖（LPS）誘導小鼠急性肺損傷（ALI）的影響，探討其可能的作用機製。方法將40隻健康雄性昆明小鼠按隨機數字錶法分為對照組、模型組及芹菜素低、中、高劑量組，每組8隻。採用腹腔註射LPS 5 mg/kg製備ALI模型；芹菜素低、中、高劑量組分彆于製模前1 h腹腔註射芹菜素10、25、50 mg/kg進行榦預。製模後6 h進行指標檢測，取右肺上葉行囌木素-伊紅（HE）染色觀察肺組織病理改變併對其進行病理評分，取右肺下葉稱重測濕/榦質量（W/D）比值，酶聯免疫吸附試驗（ELISA）檢測血清及支氣管肺泡灌洗液（BALF）中細胞間黏附分子-1（ICAM-1）和腫瘤壞死因子-α（TNF-α）的含量，逆轉錄-聚閤酶鏈反應（RT-PCR）檢測p38絲裂素活化蛋白激酶（p38MAPK）、ICAM-1和TNF-α的mRNA錶達。結果與對照組比較，模型組肺W/D比值增高（17.79±2.89比5.56±0.37，P＜0.05），肺組織病理評分增加（分：10.32±0.23比1.87±0.54，P＜0.05），血清及BALF中ICAM-1、TNF-α含量升高〔血清中ICAM-1（ng/L）：21.4±2.7比14.3±3.5，TNF-α（ng/L）：254.8±10.6比142.3±13.7；BALF 中 ICAM-1（ng/L）：20.3±2.4比11.5±3.2，TNF-α（ng/L）：230.3±5.8比110.5±11.2，均 P＜0.05〕，且 p38MAPK、ICAM-1和 TNF-α的mRNA錶達亦明顯升高（以對照組為1，p38MAPK、ICAM-1、TNF-α的相對錶達量分彆為4.42±0.37、4.89±0.27、3.28±0.13，均P＜0.05）；不同劑量芹菜素可減輕上述損傷效應，以中劑量組改善最為明顯，肺W/D比值為13.28±1.21，血清中ICAM-1為（18.5±4.3）ng/L，TNF-α為（169.4±20.8）ng/L，BALF中ICAM-1為（17.8±3.5）ng/L，TNF-α為（150.4±7.1）ng/L，肺組織p38MAPK、ICAM-1、TNF-α的mRNA錶達分彆為2.99±0.28、3.97±0.17、2.87±0.27，與模型組比較差異均有統計學意義（P＜0.05或P＜0.01）。結論芹菜素可不同程度的拮抗LPS引起的小鼠ALI，以中劑量組改善效果最好，其保護作用可能與抑製p38MAPK信號通路活化、減少TNF-α和ICAM-1等炎癥因子錶達有關。
목적：관찰근채소대지다당（LPS）유도소서급성폐손상（ALI）적영향，탐토기가능적작용궤제。방법장40지건강웅성곤명소서안수궤수자표법분위대조조、모형조급근채소저、중、고제량조，매조8지。채용복강주사LPS 5 mg/kg제비ALI모형；근채소저、중、고제량조분별우제모전1 h복강주사근채소10、25、50 mg/kg진행간예。제모후6 h진행지표검측，취우폐상협행소목소-이홍（HE）염색관찰폐조직병리개변병대기진행병리평분，취우폐하협칭중측습/간질량（W/D）비치，매련면역흡부시험（ELISA）검측혈청급지기관폐포관세액（BALF）중세포간점부분자-1（ICAM-1）화종류배사인자-α（TNF-α）적함량，역전록-취합매련반응（RT-PCR）검측p38사렬소활화단백격매（p38MAPK）、ICAM-1화TNF-α적mRNA표체。결과여대조조비교，모형조폐W/D비치증고（17.79±2.89비5.56±0.37，P＜0.05），폐조직병리평분증가（분：10.32±0.23비1.87±0.54，P＜0.05），혈청급BALF중ICAM-1、TNF-α함량승고〔혈청중ICAM-1（ng/L）：21.4±2.7비14.3±3.5，TNF-α（ng/L）：254.8±10.6비142.3±13.7；BALF 중 ICAM-1（ng/L）：20.3±2.4비11.5±3.2，TNF-α（ng/L）：230.3±5.8비110.5±11.2，균 P＜0.05〕，차 p38MAPK、ICAM-1화 TNF-α적mRNA표체역명현승고（이대조조위1，p38MAPK、ICAM-1、TNF-α적상대표체량분별위4.42±0.37、4.89±0.27、3.28±0.13，균P＜0.05）；불동제량근채소가감경상술손상효응，이중제량조개선최위명현，폐W/D비치위13.28±1.21，혈청중ICAM-1위（18.5±4.3）ng/L，TNF-α위（169.4±20.8）ng/L，BALF중ICAM-1위（17.8±3.5）ng/L，TNF-α위（150.4±7.1）ng/L，폐조직p38MAPK、ICAM-1、TNF-α적mRNA표체분별위2.99±0.28、3.97±0.17、2.87±0.27，여모형조비교차이균유통계학의의（P＜0.05혹P＜0.01）。결론근채소가불동정도적길항LPS인기적소서ALI，이중제량조개선효과최호，기보호작용가능여억제p38MAPK신호통로활화、감소TNF-α화ICAM-1등염증인자표체유관。
Objective To observe the effect of apigenin on acute lung injury (ALI) induced by lipopolysaccharide(LPS)in mice,and to discuss its possible mechanism. Methods Forty healthy male Kunming mice were randomly divided using random number table into control group,model group and low,medium,high dose groups of apigenin intervention,and each group consisted of 8 mice. The model of ALI was reproduced by intraperitoneal injection of 5 mg/kg LPS. Mice of the low,medium and high-dose intervention groups were given intraperitoneal injection of apigenin 10,25,50 mg/kg,respectively,1 hour before LPS modeling. Pathological changes in right upper lobe of lung tissue were examined after hematoxylin and eosin(HE)staining and pathology score was observed at 6 hours after modeling. Right inferior lung was weighed to measured wet/dry ratio(W/D). Intercellular adhesion molecule-1(ICAM-1)and tumor necrosis factor-α(TNF-α)in serum and bronchoalveolar lavage fluid (BALF)were determined by enzyme linked immunosorbent assay(ELISA). The mRNA expressions of p38 mitogen-activated protein kinase(p38MAPK),ICAM-1,and TNF-α were determined by reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with control group,lung W/D ratio in model group was significantly increased(17.79±2.89 vs. 5.56±0.37,P<0.05),and the pathology score was significantly elevated(10.32±0.23 vs. 1.87±0.54,P<0.05),ICAM-1 and TNF-α contents,in serum and BALF were increased〔ICAM-1(ng/L) in serum:21.4±2.7 vs. 14.3±3.5,TNF-α(ng/L)in serum:254.8±10.6 vs. 142.3±13.7;ICAM-1(ng/L)in BALF:20.3±2.4 vs. 11.5±3.2,TNF-α(ng/L)in BALF:230.3±5.8 vs. 110.5±11.2,all P<0.05〕,and the mRNA expressions of p38MAPK,ICAM-1 and TNF-α were also increased significantly(the mRNA expression of p38MAPK,ICAM-1 and TNF-αwere 4.42±0.37,4.89±0.27,3.28±0.13,respectively,all P<0.05). Different doses of apigenin could obviously alleviate the damaging effect to the lung,and the most obvious effect was seen in the medium dose group,in which lung W/D ratio was 13.28±1.21,ICAM-1 in serum was(18.5±4.3)ng/L,TNF-αin serum was(169.4±20.8)ng/L,ICAM-1 in BALF was(17.8±3.5)ng/L,TNF-αin BALF was(150.4±7.1)ng/L, the mRNA expression of p38MAPK,ICAM-1 and TNF-αin lung tissue was 2.99±0.28,3.97±0.17,2.87±0.27, respectively. Statistically significant difference was found when they were compared with that of model group(P<0.05 or P<0.01). Conclusion Different doses of apigenin have some antagonistic effect against LPS in producing ALI in mice,the best improvement effect was seen in the medium dose group,and the protective effect may be related to inhibition of p38MAPK signaling pathway activity and reduction of pro-inflammatory factors such as TNF-αand ICAM-1 expression.
