中国药科大学学报
中國藥科大學學報
중국약과대학학보
Journal of China Pharmaceutical University
2015年
5期
605-609
,共5页
脂多糖%脓毒症%自噬%雷帕霉素%3-甲基腺嘌呤
脂多糖%膿毒癥%自噬%雷帕黴素%3-甲基腺嘌呤
지다당%농독증%자서%뢰파매소%3-갑기선표령
lipopolysaccharide%sepsis%autophagy%rapamycin%3-methyladenine
为探讨自噬对脂多糖（ LPS）所致脓毒症小鼠急性肺损伤的影响，采用健康昆明小鼠随机分为空白组、模型组（LPS，10 mg／kg），雷帕霉素组（RAP，6 mg／kg），RAP-LPS 组（RAP 6 mg／kg ＋LPS 10 mg／kg），3-甲基腺嘌呤组（3-MA，300μg／kg）和3-MA-LPS组（3-MA 300μg／kg＋LPS 10 mg／kg），腹腔注射，给药6 h后，检测小鼠死亡率、肺组织中性粒细胞浸润、以及TNF-α、LC3和P62的表达。结果显示在LPS组中，小鼠肺组织中性粒细胞浸润显著增多，死亡率增加，TNF-α、LC3-Ⅱ和P62表达升高；RAP-LPS组较模型组死亡率下降，中性粒细胞浸润、P62和TNF-α均减少，而LC3-Ⅱ略升高；在3-MA-LPS组中，LC3-Ⅱ较LPS组降低，而中性粒细胞浸润、P62和TNF-α则没有差异。结果表明在LPS所致的脓毒症中，小鼠肺组织存在自噬流阻断，自噬体成熟障碍，RAP则能逆转LPS所致的肺组织自噬流障碍，改善细胞内环境，减轻炎性反应，降低死亡率。
為探討自噬對脂多糖（ LPS）所緻膿毒癥小鼠急性肺損傷的影響，採用健康昆明小鼠隨機分為空白組、模型組（LPS，10 mg／kg），雷帕黴素組（RAP，6 mg／kg），RAP-LPS 組（RAP 6 mg／kg ＋LPS 10 mg／kg），3-甲基腺嘌呤組（3-MA，300μg／kg）和3-MA-LPS組（3-MA 300μg／kg＋LPS 10 mg／kg），腹腔註射，給藥6 h後，檢測小鼠死亡率、肺組織中性粒細胞浸潤、以及TNF-α、LC3和P62的錶達。結果顯示在LPS組中，小鼠肺組織中性粒細胞浸潤顯著增多，死亡率增加，TNF-α、LC3-Ⅱ和P62錶達升高；RAP-LPS組較模型組死亡率下降，中性粒細胞浸潤、P62和TNF-α均減少，而LC3-Ⅱ略升高；在3-MA-LPS組中，LC3-Ⅱ較LPS組降低，而中性粒細胞浸潤、P62和TNF-α則沒有差異。結果錶明在LPS所緻的膿毒癥中，小鼠肺組織存在自噬流阻斷，自噬體成熟障礙，RAP則能逆轉LPS所緻的肺組織自噬流障礙，改善細胞內環境，減輕炎性反應，降低死亡率。
위탐토자서대지다당（ LPS）소치농독증소서급성폐손상적영향，채용건강곤명소서수궤분위공백조、모형조（LPS，10 mg／kg），뢰파매소조（RAP，6 mg／kg），RAP-LPS 조（RAP 6 mg／kg ＋LPS 10 mg／kg），3-갑기선표령조（3-MA，300μg／kg）화3-MA-LPS조（3-MA 300μg／kg＋LPS 10 mg／kg），복강주사，급약6 h후，검측소서사망솔、폐조직중성립세포침윤、이급TNF-α、LC3화P62적표체。결과현시재LPS조중，소서폐조직중성립세포침윤현저증다，사망솔증가，TNF-α、LC3-Ⅱ화P62표체승고；RAP-LPS조교모형조사망솔하강，중성립세포침윤、P62화TNF-α균감소，이LC3-Ⅱ략승고；재3-MA-LPS조중，LC3-Ⅱ교LPS조강저，이중성립세포침윤、P62화TNF-α칙몰유차이。결과표명재LPS소치적농독증중，소서폐조직존재자서류조단，자서체성숙장애，RAP칙능역전LPS소치적폐조직자서류장애，개선세포내배경，감경염성반응，강저사망솔。
This study was designed to examine the effects of autophagy on the lipopolysaccharide(LPS)-induced acute lung injury (ALI)and to analyze the possible mechanism.Kunming mice of clean grade were randomly divided into 6 groups:control group(saline;ip);model group(LPS 10 mg/kg;ip);RAP group(rapamycin 6 mg/kg;ip);RAP+LPS group (RAP 6 mg/kg and LPS 10 mg/kg;ip);3-MA group (3-methyladenine 300 μg/kg;ip);and 3-MA+LPS group (3-MA 300 μg/kg and LPS 10 mg/kg;ip).6 h after LPS injection;mortality was checked.Neutrophil aggregation;and the expressions of TNF-α;LC3 and P62 in lung tissue were checked by fluo-rescence microscopy and Western blot.The results revealed a higher mortality;neutrophil infiltration and TNF-αexpression and significantly increased levels of autophagy marker LC3-II and P62 in LPS group;in RAP+LPS group;pretreatment with RAP notably reversed LPS-induced neutrophil infiltration and TNF-αexpression;LC3-II were further slightly increased;while P62 was significantly decreased;in 3-MA+LPS group;pretreatment of 3-MA slightly decreased LC3-II expression;P62;neutrophil infiltration and TNF-αremained almost the same to those in LPS group.These data suggesed that;in sepsis;autophagy flux in the lung tissue is partially blocked;and RAP help to alleviate LPS-induced lung injury;which might through promoting autophagosome maturation;smoothing autophagy flux;and eventually to mitigate pulmonary inflammation.
