Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System
Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System
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Exendin-4 通过激活交感神经系统加剧小鼠烧伤诱发的发病率
DOI：
10.1155/2019/2750528
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Yao YM
中科院分区：
文献类型：
--
作者：
Ji XJ;Hao JW;Li GL;Dong N;Wang XQ;Zhou M;Zhang QH;Yao YM
背景：尽管基于胰升糖素样肽1(GLP-1)的烧伤高血糖治疗已在临床试验中显示出巨大的潜力，但其安全性很少被评价。我们推测，Exendin-4，一个GLP-1类似物，可能通过激活烧伤时的交感神经系统来影响免疫反应。方法雄性Balb/c小鼠造成15%体表面积的假烫伤或烫伤。用β受体拮抗剂心得安(1 /L)或Exendin(9-39)(1 μ/L)体外培养脾细胞，观察Exendin-4对T细胞功能的影响。给小鼠注射Exendin-4(2.4nmoL/kg)。为进一步阐明交感神经机制，伤前30 给予心得安(30 mg/kg)或溶媒。结果心得安可加重Exendin-4致烧伤小鼠死亡率，但心得安(9-39)可恢复exendin-4对T细胞增殖的抑制作用。然而，Exendin-4在体外引起的Th2转换只能被Exendin(9-39)逆转。普奈洛尔可恢复exendin-4对小鼠脾T细胞功能和NFAT活性的抑制作用。相比之下，心得安可增强假手术组小鼠脾组织中Exendin-4增加的NF-κB转位，但对烧伤组小鼠有抑制作用。因此，心得安可减轻烧伤小鼠肺组织炎症反应的增强和exendin-4所致的器官损伤。相反，心得安可增强烧伤小鼠Th2细胞的转换和由exendin-4引起的较高的血清炎症介质水平。Exendin-4可提高血清应激激素水平，而心得安可显著提高应激激素水平。结论Exendin-4通过激活交感神经系统抑制T细胞功能，促进器官炎症，而通过GLP-1R诱导Th2转换。
Background Although glucagon-like peptide 1- (GLP-1-) based therapy of hyperglycemia in burn injury has shown great potential in clinical trials, its safety is seldom evaluated. We hypothesize that exendin-4, a GLP-1 analogue, might affect the immune response via the activation of the sympathetic nervous system in burn injury. Methods Male Balb/c mice were subjected to sham or thermal injury of 15% total body surface area. Exendin-4 on T cell function in vitro was examined in cultured splenocytes in the presence of β-adrenoceptor antagonist propranolol (1 nmol/L) or GLP-1R antagonist exendin (9-39) (1 μmol/L), whereas its in vivo effect was determined by i.p. injection of exendin-4 (2.4 nmol/kg) in mice. To further elucidate the sympathetic mechanism, propranolol (30 mg/kg) or vehicle was applied 30 min prior to injury. Results Although the exacerbated burn-induced mortality by exendin-4 was worsened by propranolol pretreatment, the inhibition of T cell proliferation by exendin-4 in vitro could be restored by propranolol instead of exendin (9-39). However, a Th2 switch by exendin-4 in vitro could only be reversed by exendin (9-39). Likewise, the inhibition of splenic T cell function and NFAT activity by exendin-4 in vivo was restored by propranolol. By contrast, the increased splenic NF-κB translocation by exendin-4 in vivo was potentiated by propranolol in sham mice but suppressed in burn mice. Accordingly, propranolol abrogated the heightened inflammatory response in the lung and the accelerated organ injuries by exendin-4 in burn mice. On the contrary, a Th2 switch and higher serum levels of inflammatory mediators by exendin-4 were potentiated by propranolol in burn mice. Lastly, exendin-4 raised serum stress hormones which could be remarkably augmented by propranolol. Conclusions Exendin-4 suppresses T cell function and promotes organ inflammation through the activation of the sympathetic nervous system, while elicits Th2 switch via GLP-1R in burn injury.
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影响因子：
15.1
作者：
Sanders, Virginia M.
通讯作者：
Sanders, Virginia M.
DOI：
10.1186/cc9222
发表时间：
2010
期刊：
Critical care (London, England)
影响因子：
--
作者：
Mecott GA;Herndon DN;Kulp GA;Brooks NC;Al-Mousawi AM;Kraft R;Rivero HG;Williams FN;Branski LK;Jeschke MG
通讯作者：
Jeschke MG
Exendin-4（一种胰高血糖素样肽-1 类似物）对 2 型糖尿病患者的人外周淋巴细胞的抗炎作用。
影响因子：
3.2
作者：
He L;Wong CK;Cheung KK;Yau HC;Fu A;Zhao HL;Leung KM;Kong AP;Wong GW;Chan PK;Xu G;Chan JC
通讯作者：
Chan JC
影响因子：
9.3
作者：
Zhang QH;Chen Q;Kang JR;Liu C;Dong N;Zhu XM;Sheng ZY;Yao YM
通讯作者：
Yao YM
影响因子：
8.2
作者：
Lee, Y. -S.;Park, M. -S.;Jun, H. -S.
通讯作者：
Jun, H. -S.