氯喹减轻重症急性胰腺炎肝损伤的机制研究  

Mechanism of effect of chloroquine on relief of liver injury in rats with severe acute pancreatitis

作　　者：张磊[1] 吴河水[2] 陈孝平[1] 张万广[1] 王春友[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科中心,湖北武汉430030 [2]华中科技大学同济医学院附属协和医院胰腺外科中心,湖北武汉430022

出　　处：《中国普通外科杂志》2009年第7期740-743,共4页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(30200272)

摘　　要：目的探讨氯喹(CQ)减轻重症急性胰腺炎(SAP)肝损伤作用的机制。方法60只Wistar雄性大鼠分为假手术组,SAP组,L-Arg治疗组,L-NAME治疗组,CQ治疗组,CQ+L-NAME治疗组,每组各10只。RT-PCR和Western Blot检测肝组织TLR4的表达。结果SAP组肝组织TLR4表达明显增高,一氧化氮(NO)浓度降低,肝损伤加重(P<0.05)。L-Arg组NO升高,TLR4表达受抑,肝损伤减轻(P<0.05)。L-NAME组NO明显抑制,肝组织TLR4表达升高,肝损伤加重(P<0.05)。CQ组TLR4表达降低,肝组织NO升高,肝损伤减轻(P<0.05)。CQ+L-NAME组肝组织NO明显降低,TLR4升高,肝损伤加重(P<0.05)。结论TLR4表达上调在SAP肝损伤的发生、发展中可能有重要作用。CQ可能通过提高NO的合成和释放而抑制TLR4的表达,减轻SAP并发肝损伤。Objective To study the mechanism of chloroquine （ CQ ） on relief of liver injury in severe acute pancreatitis （SAP）. Methods Sixty Wistar male rats were randomized into sham-operated, SAP, L-Arg-treated, L-NAME-treated, CQ-treated and CQ ＋ L-NAME-treated group. Expression of TLR4 was detected using RT-PCR and Western Blot. Results TLR4 expression was markedly increased in SAP （ P 〈 0.05）. Liver injury was increased, and NO concentration was decreased （ P 〈 0. 05 ）. When TLR4 was inhibited by L-Arg or stimulated by L-NAME, liver injury was relieved or increased （ P 〈 0. 05 ）. CQ inhibited expression of TLR4, increased production of NO, and subsequently relieved liver injury （ P 〈 0.05）. When rats with SAP were injected with CQ and L-NAME, NO concentration was markedly decreased, the effect of CQ on inhibiting TLR4 expression was markedly weakened （ P 〈 0.05 ） , and liver injury was increased. Conclusions TLR4 expression might play an important role in pathogenesis and d evelopment of liver injury in SAP. The inhibition of TLR4 expression from CQ could be via the pathway of increasing production and release of NO, which can result in relief of liver injury in SAP rats.

关 键 词：胰腺炎 急性坏死性/药物疗法 TOLL样受体 肝/病理学 氯喹 一氧化氮 

分 类 号：R657.5[医药卫生—外科学]