Saquinavir Ameliorates Liver Warm Ischemia-Reperfusion-Induced Lung Injury via HMGB-1- and P38/JNK-Mediated TLR-4-Dependent Signaling Pathways.
Saquinavir Ameliorates Liver Warm Ischemia-Reperfusion-Induced Lung Injury via HMGB-1- and P38/JNK-Mediated TLR-4-Dependent Signaling Pathways.
复制标题
沙奎那韦通过 HMGB-1 和 P38/JNK 介导的 TLR-4 依赖性信号通路改善肝脏热缺血再灌注引起的肺损伤
DOI：
10.1155/2017/7083528
复制
发表时间：
2017
影响因子：
4.6
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yu Z;Tong Y;Zhang R;Ding X;Li Q
肝脏缺血和再灌注（I/R）可引起局部和远处组织损伤，在更广泛的病理中导致发病率和死亡率。这在不受控制的无菌性炎症条件下尤其常见，导致远端器官损伤，如肺损伤，甚至衰竭。沙奎那韦（SQV）是一种具有抗炎作用的HIV蛋白酶抑制剂。在这项研究中，我们研究了SQV是否抑制toll样受体4- (TLR4-)依赖的高迁移率组盒1 （HMGB1）和P38/JNK信号通路，从而保护小鼠肝I/ r诱导的肺损伤。为了验证我们的假设，我们使用C57BL/6小鼠和TLR4敲除小鼠（TLR4−/−）进行研究。在肝缺血1小时和再灌注6小时后，给药SQV可明显减轻远端肺组织损伤。正如我们所料，SQV减轻了I/ r诱导的肺水肿、高通透性和病理损伤。SQV的有益作用与循环和肺组织炎症因子水平的降低有关，如IL-6、IL-1β、TNF-α和iNOS。在野生型肝I/R小鼠中，SQV的保护作用还与肺组织HMGB1、TLR-4和p-P38/JNK的表达降低有关，但与p-ERK无关。总之，本研究证明了SQV的新作用，促进HMGB1-和P38/ jnk介导的tlr -4依赖性信号通路的负调控，从而保护肝脏免受I/ r诱导的肺损伤。
Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4−/−) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1β, TNF-α, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.
登录
查看更多内容
WISP1通过TLR4信号介导小鼠肝脏热缺血再灌注损伤
影响因子：
4.6
作者：
Tong Y;Ding XB;Chen ZX;Jin SQ;Zhao X;Wang X;Mei SY;Jiang X;Wang L;Li Q
通讯作者：
Li Q
影响因子：
37.8
作者：
Oyama, J;Blais, C;Bourcier, T
通讯作者：
Bourcier, T
影响因子：
3.6
作者：
Groeneveld, ABJ;Verheij, J;Rauwerda, JA
通讯作者：
Rauwerda, JA
影响因子：
13.5
作者：
Nace, Gary W.;Huang, Hai;Klune, John R.;Eid, Raymond E.;Rosborough, Brian R.;Korff, Sebastian;Li, Shen;Shapiro, Richard A.;Stolz, Donna B.;Sodhi, Chhinder P.;Hackam, David J.;Geller, David A.;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
影响因子：
6.7
作者：
Gianni T;Campadelli-Fiume G
通讯作者：
Campadelli-Fiume G