Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction.
Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction.
复制标题
ATP敏感钾通道Kir6.2亚基在内毒素血症所致心功能障碍中的作用
DOI：
10.1186/1475-2840-12-75
复制
发表时间：
2013-05-09
影响因子：
9.3
通讯作者：
Shen FM
中科院分区：
文献类型：
--
作者：
Yang ZW;Chen JK;Ni M;Zhao T;Deng YP;Tao X;Jiang GJ;Shen FM
背景
心功能不全在内毒素血症中得到了很好的描述，在高达60%的内毒素休克患者中得到了诊断。ATP敏感性钾通道（KATP）对心脏功能至关重要。本研究探讨KATP通道Kir6.2亚基在脂多糖（LPS）诱导的内毒素血症心功能不全中的作用。
方法
Kir6.2亚基敲除（Kir6.2−/−）和野生型（WT）小鼠注射LPS以诱导内毒素血症。超声心动图监测心功能。取左心室进行显微镜（光镜和电镜）和TUNEL检查。测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活性及血清和左心室组织肿瘤坏死因子-α（TNF-α）水平。
结果
与WT相比，Kir6.2−/−小鼠在LPS给药后360 min表现出显著的心功能下降，心肌损伤加重，血清LDH和CK活性升高。在90、180和360 min时，Kir6.2 −/−小鼠心脏组织中凋亡细胞明显增加。Kir6.2−/−小鼠血清和心脏组织中TNF-α表达均显著增加。
结论
我们的结论是Kir6.2亚基是关键的抵抗内毒素血症引起的心功能不全，通过抑制细胞凋亡和炎症减少心肌损伤。KATP通道阻滞剂广泛应用于糖尿病的治疗，因此，当使用磺脲类降糖药物治疗的患者并发内毒素血症时，应考虑其潜在的作用。
Background
Cardiac dysfunction is well-described in endotoxemia and diagnosed in up to 60% of patients with endotoxic shock. ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia.
Methods
Kir6.2 subunits knockout (Kir6.2−/−) and wild-type (WT) mice were injected with LPS to induce endotoxemia. Cardiac function was monitored by echocardiography. Left ventricles were taken for microscopy (both light and electron) and TUNEL examination. Serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, and tumor necrosis factor-α (TNF-α) levels in both serum and left ventricular tissues were determined.
Results
Compared to WT, Kir6.2−/− mice showed significantly declined cardiac function 360 min after LPS administration, aggravated myocardial damage and elevated serum LDH and CK activities. Apoptotic cells were obviously increased in heart tissues from Kir6.2−/− mice at 90, 180 and 360 min. TNF-α expression in both serum and heart tissues of Kir6.2−/− mice was significantly increased.
Conclusions
We conclude that Kir6.2 subunits are critical in resistance to endotoxemia-induced cardiac dysfunction through reducing myocardial damage by inhibition of apoptosis and inflammation. KATP channels blockers are extensively used in the treatment of diabetes, their potential role should therefore be considered in the clinic when patients treated with antidiabetic sulfonylureas are complicated by endotoxemia.
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影响因子：
9.3
作者：
Chen ZC;Cheng YZ;Chen LJ;Cheng KC;Li Y;Cheng J
通讯作者：
Cheng J
DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B
影响因子：
37.8
作者：
Lancel, S;Joulin, O;Neviere, R
通讯作者：
Neviere, R
DOI：
10.1152/ajpheart.00348.2001
发表时间：
2002-04-01
影响因子：
4.8
作者：
Liu, HP;Zhang, HY;Yao, ZH
通讯作者：
Yao, ZH
影响因子：
20.3
作者：
Lamkanfi, Mohamed;Moreira, Lilian O.;Kanneganti, Thirumala-Devi
通讯作者：
Kanneganti, Thirumala-Devi