Department of Pediatrics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, No. 15 Jiefang Road, Xiangyang, 441000, Hubei Province, People's Republic of China.
Inflammation. 2019 Dec;42(6):2170-2180. doi: 10.1007/s10753-019-01081-3.
Sepsis-induced myocardial dysfunction (SIMD), lack of effective treatment, accounts for high mortality of sepsis. Mitochondrion-targeted antioxidant peptide SS31 has been revealed to be responsible for certain cardiovascular disease by ameliorating oxidative stress injury. But whether it protects a septic heart remains little known. This study sought to prove that SS31 was capable of improving sepsis-induced myocardial dysfunction dramatically. C57BL/6 mice were intraperitoneally administered lipopolysaccharide (LPS), exposed to systemic inflammation. Thirty-five C57BL/6 mice were randomly divided into four groups: sham group, LPS group (5 mg/kg), SS31 group (5 mg/kg), and SS31 + LPS group (treatment group). Heart tissues were harvested for pathological examination at the indicated time points. H9C2 cell were treated with LPS with or without the presence of SS31 (10 μM) at 37 °C to assess the effect on cardiomyocytes at the indicated time points. SS31 restored myocardial morphological damage and suppressed inflammatory response as evidenced by significantly decreasing the mRNA levels of IL-6, IL-1β, and TNF-α in vitro and in vivo. In addition, myocardial energy deficiency secondary to sepsis was remarkedly ameliorated by SS31. Furthermore, we found that SS-31 normalized the activity of malondialdehyde, glutathione peroxidase, and superoxide dismutase in vitro and in vivo, and maintained mitochondrial membrane potential (MMP) as well. And western blot was applied to measure the expressions of p-p38MAPK, p-JNK1/2, p-ERK, p62, and NF-κB p65; the results illuminated that the cardioprotective effect of SS31 was partly linked to NF-κB. In conclusion, SS31 therapy effectively protected the heart against LPS-induced cardiac damage.
脓毒症诱导的心肌功能障碍（SIMD）缺乏有效治疗，导致脓毒症死亡率居高不下。已发现靶向线粒体的抗氧化肽 SS31 通过改善氧化应激损伤而对某些心血管疾病负责。但它是否对脓毒症心脏有保护作用还知之甚少。本研究旨在证明 SS31 能够显著改善脓毒症引起的心肌功能障碍。C57BL/6 小鼠腹腔内给予脂多糖（LPS），暴露于全身炎症。35 只 C57BL/6 小鼠随机分为四组：假手术组、LPS 组（5mg/kg）、SS31 组（5mg/kg）和 SS31+LPS 组（治疗组）。在指定时间点收获心脏组织进行病理检查。H9C2 细胞在 37°C 下用 LPS 处理，有或没有 SS31（10μM）处理，以评估在指定时间点对心肌细胞的影响。SS31 恢复了心肌形态损伤，并抑制了炎症反应，体外和体内均显著降低了 IL-6、IL-1β 和 TNF-α 的 mRNA 水平。此外，SS31 显著改善了脓毒症引起的心肌能量不足。此外，我们发现 SS-31 使丙二醛、谷胱甘肽过氧化物酶和超氧化物歧化酶的活性在体外和体内均恢复正常，并维持线粒体膜电位（MMP）。并应用 Western blot 测量 p-p38MAPK、p-JNK1/2、p-ERK、p62 和 NF-κB p65 的表达；结果表明，SS31 的心脏保护作用部分与 NF-κB 有关。总之，SS31 治疗可有效保护心脏免受 LPS 诱导的心脏损伤。
