高龄加剧烫伤烧伤小鼠模型的肝损伤。
Advanced age heightens hepatic damage in a murine model of scald burn injury.
机构信息
From the Division of G.I., Trauma, and Endocrine Surgery, (J.-P.I., D.M.B. S.K., T.W., R.H.M., E.J.K.), Division of Burn Research, Department of Surgery (D.M.B., T.W., R.H.M., E.J.K.), Department of Immunology and Microbiology (D.M.B., T.W., E.J.K.), Division of Alcohol Research, Department of Surgery (R.H.M., E.J.K.), University of Colorado, Aurora, Colorado.
出版信息
J Trauma Acute Care Surg. 2021 Apr 1;90(4):731-737. doi: 10.1097/TA.0000000000003048.
BACKGROUND
Elderly burn patients exhibit a lower survival rate compared with younger counterparts. The liver is susceptible to damage after burn injury, which predisposes to poor outcomes. Lipid homeostasis and the antioxidant glutathione system play fundamental roles in preserving liver integrity. Herein, we explored changes in these major pathways associated with liver damage in the aging animals after burn injury.
METHODS
We compared liver enzymes, histology, lipid-peroxidation, and glutathione-metabolism profiles from young and aged female mice after a 15% total body surface area burn. Mice were euthanized at 24 hours after injury, and livers and serum were collected.
RESULTS
Aged burn animals exhibited elevated (p < 0.05) aspartate aminotransferase and alanine aminotransferase levels and increased inflammatory cell infiltration, edema, and necrosis compared with their younger counterparts. The percentage of adipophilin-stained area in livers from young sham, young burn, aged sham, and aged burn groups was 10%, 44%, 16%, and 78% (p < 0.05), respectively. Liver malondialdehyde levels were 1.4 ± 0.5 nmol/mg, 2.06 ± 0.2 nmol/mg, 1.81 ± 0.12 nmol/mg, and 3.45 ± 0.2 nmol/mg (p < 0.05) in young sham, young burn, aged sham, and aged burn mice, respectively. Oxidized glutathione (GSSG) content increased 50% in the young burn, and 88% in aged burn animals compared with the young sham group (p < 0.05). The reduced glutathione GSH/GSSG ratio was significantly reduced by 54% in aged burn mice compared with young sham animals (p < 0.05). Furthermore, glutathione peroxidase gene expression showed a 96% decrease in the aged burn group compared with young sham mice (p < 0.05).
CONCLUSION
Aged burn animals exhibit severe liver damage from heightened lipid peroxidation and inadequate antioxidative response. The increased peroxidation is associated with abundant lipid deposits in hepatic tissue postburn and a weak antioxidative response due to hepatic glutathione peroxidase downregulation. Further studies will focus on the functional significance of these findings concerning hepatic homeostasis.
背景
与年轻患者相比，老年烧伤患者的存活率较低。烧伤后肝脏容易受损，导致预后不良。脂质稳态和抗氧化谷胱甘肽系统在维持肝脏完整性方面发挥着重要作用。在此，我们探讨了这些与烧伤后老年动物肝脏损伤相关的主要途径的变化。
方法
我们比较了年轻和老年雌性小鼠在体表面积 15%烧伤后 24 小时的肝脏酶、组织学、脂质过氧化和谷胱甘肽代谢谱。在受伤后 24 小时处死小鼠，采集肝脏和血清。
结果
与年轻烧伤动物相比，老年烧伤动物的天门冬氨酸转氨酶和丙氨酸转氨酶水平升高（p < 0.05），炎症细胞浸润、水肿和坏死增加。年轻假手术、年轻烧伤、老年假手术和老年烧伤组肝脏中脂联素染色面积百分比分别为 10%、44%、16%和 78%（p < 0.05）。年轻假手术、年轻烧伤、老年假手术和老年烧伤组肝脏丙二醛水平分别为 1.4 ± 0.5 nmol/mg、2.06 ± 0.2 nmol/mg、1.81 ± 0.12 nmol/mg 和 3.45 ± 0.2 nmol/mg（p < 0.05）。与年轻假手术组相比，年轻烧伤组和老年烧伤组的氧化型谷胱甘肽（GSSG）含量分别增加了 50%和 88%（p < 0.05）。与年轻假手术动物相比，老年烧伤组的还原型谷胱甘肽 GSH/GSSG 比值降低了 54%（p < 0.05）。此外，与年轻假手术组相比，老年烧伤组的谷胱甘肽过氧化物酶基因表达降低了 96%（p < 0.05）。
结论
老年烧伤动物的肝脏损伤严重，脂质过氧化增加，抗氧化反应不足。增加的过氧化与肝组织中大量的脂质沉积以及肝谷胱甘肽过氧化物酶下调导致的抗氧化反应减弱有关。进一步的研究将集中于这些发现对肝脏稳态的功能意义。
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