Tao Bingdong, Liu Lidan, Wang Ni, Tong Dongyi, Wang Wei, Zhang Jin
*Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, P.R. China †Department of Anesthesiology, General Hospital of Shenyang Military Region, Shenyang, P.R. China.
Shock. 2015 Dec;44(6):593-600. doi: 10.1097/SHK.0000000000000467.
Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.
脓毒症在重症监护病房（ICU）中很常见，且与高死亡率相关。脓毒症并发的心脏功能障碍是导致这种死亡率的最重要原因之一。这种功能障碍是由于心肌炎症和心脏能量产生减少所致。多项研究表明，富氢盐水（HRS）对脓毒症有有益作用。因此，我们测试了HRS是否通过增加心脏能量来预防心脏功能障碍。四组大鼠腹腔注射以下溶液之一：生理盐水（NS）、HRS、脂多糖（LPS）和LPS加HRS。注射后8小时通过超声心动图测量心脏功能。通过定量聚合酶链反应（PCR）和蛋白质印迹分析测量与脂肪酸氧化（FAO）相关的基因和蛋白质表达。注射LPS通过降低缩短分数（FS）和增加左心室直径（LVD）损害心脏功能。添加HRS可增加FS、棕榈酸三磷酸以及磷酸肌酸（PCr）与三磷酸腺苷（ATP）的比率，并减小LVD。LPS刺激降低了与FAO相关基因的表达，包括过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、过氧化物酶体增殖物激活受体α（PPARα）、雌激素相关受体α（ERRα）及其下游靶点，在mRNA和蛋白质水平上，HRS可减轻这种降低。然而，HRS对葡萄糖代谢影响很小。此外，HRS抑制大鼠心脏中的c-Jun氨基末端激酶（JNK）激活。HRS对JNK的抑制至少部分地通过恢复心脏FAO对LPS刺激的大鼠显示出有益作用。
