Chloroquine relieves acute lung injury in rats with acute hemorrhagic necrotizing pancreatitis.

Chloroquine relieves acute lung injury in rats with acute hemorrhagic necrotizing pancreatitis.
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氯喹缓解急性出血坏死性胰腺炎大鼠急性肺损伤

DOI:
10.1007/s11596-013-1124-9
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发表时间:
2013-06
期刊:
Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban
影响因子:
--
通讯作者:
Wu HS
Wu HS
中科院分区:
其他
文献类型:
--
作者:
Zhang L;Chen Y;Wang L;Chen XP;Zhang WG;Wang CY;Wu HS

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本研究初步探讨了氯喹(CQ)减轻急性出血坏死性胰腺炎(AHNP)并发急性肺损伤(ALI)的机制。雄性Wistar大鼠60只,随机分为假手术组(A组,n=10)、AHNP组(B组,n=10)、L-精氨酸治疗组(C组,n=10)、L-N-硝基-L-精氨酸甲酯(NAME)治疗组(D组,n=10)、CQ治疗组(E组,n=10)和CQ+L-NAME治疗组(F组,n=10)。分别采用真实的时间PCR和Western blotting检测TLR 4的表达。结果显示,与A组相比,B组肺组织TLR 4表达及TNF-α、IL-6水平显著升高,一氧化氮(NO)浓度显著降低(P<0.05或P<0.01)。肺损伤随着TLR 4表达的增加而加重。分别加入TLR 4抑制剂和刺激剂L-Arg和L-NAME后,肺损伤相应减轻或加重(P<0.05或P<0.01)。E组TLR 4表达明显低于B组(P<0.05或P<0.01),NO含量明显高于B组(P<0.05或P<0.01)。F组NO浓度明显降低,CQ对TLR 4表达的抑制作用及对肺损伤的缓解作用均较E组减弱(P<0.05或P<0.01)。结论TLR 4在AHNP并发ALI的发生发展中可能起重要作用。CQ可通过降低TLR 4的表达和增加NO的释放而减轻ALI。
This study preliminarily investigated the mechanism by which chloroquine (CQ) relieves acute lung injury (ALI) complicated in acute hemorrhagic necrotizing pancreatitis (AHNP). Sixty male Wistar rats were randomized into sham-operated group (group A, n=10), AHNP group (group B, n=10), L-arginine-treated group (group C, n=10), L-N-nitro-L-arginine methyl ester (NAME)-treated group (group D, n=10), CQ-treated group (group E, n=10) and CQ+L-NAME-treated group (group F, n=10). TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide (NO) concentration was reduced, as compared with those in the group A (P<0.05 or P<0.01). Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated (P<0.05 or P<0.01). In the group E, TLR4 expression was substantially lower and NO concentration higher than those in the group B (P<0.05 or P<0.01). However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E (P<0.05 or P<0.01). It was concluded that TLR4 may play an important role in the pathogenesis and development of ALI complicated in AHNP. CQ could relieve ALI by decreasing the TLR4 expression and increasing the NO release.
DOI: 10.1016/j.cgh.2009.08.012
发表时间: 2009-11-01
影响因子: 12.6
作者:
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DOI: 10.1097/01.mpa.0000163178.37050.0d
发表时间: 2005-07-01
期刊: PANCREAS
影响因子: 2.9
作者:
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