关键词: 8-epi-PGF2α CLP MIF TLR4 TNF-α cardiac ghrelin sepsis

Mesh : Animals Mice Male Ghrelin / blood Endotoxemia / blood drug therapy Cardiotonic Agents / pharmacology therapeutic use Tumor Necrosis Factor-alpha / blood Toll-Like Receptor 4 / metabolism Disease Models, Animal Dinoprost / analogs & derivatives blood Macrophage Migration-Inhibitory Factors / blood Sepsis / drug therapy complications Antioxidants / pharmacology

来  源:   DOI:10.25122/jml-2023-0228   PDF(Pubmed)

Abstract:
This study aimed to evaluate the cardioprotective effects of ghrelin in septic mice, focusing on its anti-inflammatory and antioxidant properties. Thirty-five male Swiss mice (8-12 weeks old, 23-33g) were randomly assigned to five groups (n = 7 each): (1) Normal, fed usual diets, (2) Sham, subjected to anesthesia and laparotomy, (3) Sepsis, subjected to cecal ligation and puncture, (4) Vehicle, given an equivalent volume of intraperitoneal saline injections immediately after cecal ligation and puncture, and (5) Ghrelin-treated, administered 80 µg/kg ghrelin intraperitoneal injections immediately following cecal ligation and puncture. Serum levels of tumor necrosis factor-alpha (TNF-α), macrophage migration inhibitory factor (MIF), toll-like receptor 4 (TLR4), and 8-epi-prostaglandin F2 alpha (8-epi-PGF2α) were measured. The extent of cardiac damage was also evaluated histologically. The mean serum levels of TNF-α, MIF, TLR4, and 8-epi-PGF2α levels were significantly higher in the sepsis and vehicle groups than in the normal and sham groups. The levels were significantly lower in the ghrelin-treated group than in the vehicle and sepsis groups. Histological analysis revealed normal myocardial architecture in the normal and sham groups, whereas the sepsis and vehicle groups had severe myocardial injury. The ghrelin-treated group displayed histological features similar to the sham group, indicating reduced myocardial damage. Ghrelin ameliorated sepsis-induced cardiotoxicity in mice by exhibiting strong anti-inflammatory and antioxidant effects. These findings suggest that ghrelin may be a promising therapeutic candidate for the prevention of sepsis-induced cardiotoxicity.
摘要:
本研究旨在评估ghrelin对脓毒症小鼠的心脏保护作用。专注于其抗炎和抗氧化性能。35只雄性瑞士小鼠(8-12周龄,23-33g)随机分为五组(每组n=7):(1)正常,通常的饮食,(2)Sham,接受麻醉和剖腹手术,(3)脓毒症,接受盲肠结扎和穿刺,(4)车辆,盲肠结扎和穿刺后立即给予等量的腹膜内生理盐水注射,和(5)Ghrelin处理,盲肠结扎和穿刺后立即腹膜内注射80µg/kg生长素释放肽。血清肿瘤坏死因子-α(TNF-α)水平,巨噬细胞移动抑制因子(MIF),toll样受体4(TLR4),测定8-epi-前列腺素F2α(8-epi-PGF2α)。还对心脏损伤的程度进行了组织学评估。平均血清TNF-α水平,MIF,脓毒症和媒介物组的TLR4和8-epi-PGF2α水平明显高于正常和假手术组。生长素释放肽治疗组的水平显著低于媒介物和败血症组。组织学分析显示正常组和假手术组的心肌结构正常,而脓毒症和溶媒组有严重的心肌损伤。生长素释放肽治疗组表现出与假手术组相似的组织学特征,表明心肌损伤减少。Ghrelin通过表现出强抗炎和抗氧化作用改善小鼠脓毒症诱导的心脏毒性。这些发现表明ghrelin可能是预防败血症引起的心脏毒性的有希望的治疗候选物。
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