5-氨基乙酰丙酸联合亚铁改善小鼠脂肪肝模型中的缺血再灌注损伤。
5-Aminolevulinic acid combined with ferrous iron ameliorate ischemia-reperfusion injury in the mouse fatty liver model.
作者信息
Li Shaowei, Takahara Terumi, Li Xiao-Kang, Fujino Masayuki, Sugiyama Toshiro, Tsukada Kazuhiro, Liu Chi, Kakuta Yoichi, Nonomura Norio, Ito Hidenori, Takahashi Kiwamu, Nakajima Motowo, Tanaka Tohru, Takahara Shiro
机构信息
Division of Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan; Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan; Second Department of Surgery, University of Toyama, Toyama, Japan; Clinical Medicine Research Center of Affiliated Hospital, Inner Mongolia Medical University, Hohhot, China.
Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
出版信息
Biochem Biophys Res Commun. 2016 Feb 19;470(4):900-6. doi: 10.1016/j.bbrc.2016.01.136. Epub 2016 Jan 26.
BACKGROUND
The fatty liver could increase the risk of serious acute ischemia reperfusion (I/R) injury, and hepatic steatosis is indeed a major risk factor for hepatic failure after grafting a fatty liver.
MATERIALS & METHODS: Fatty liver models of methionine- and choline-deficient high-fat mice were subjected to I/R injury with or without 5-aminolevulinic acid (5-ALA)/sodium ferrous citrate (SFC) treatment. Levels of hepatic enzymes, lipid peroxidation and apoptosis, inflammatory cytokines and heme oxygenase (HO)-1, and the carbon monoxide (CO) in the liver, and reactive oxygen species (ROS), inflammatory cytokines and members of the signaling pathway in isolated Kupffer were assessed.
RESULTS
Alanine aminotransferase and aspartate aminotransferase levels, the number of necrotic areas, thiobarbituric acid reactive substance content, TUNEL-positive cells, infiltrated macrophages, and the inflammatory cytokine expression after I/R injury were dramatically decreased, whereas the endogenous CO concentrations and the HO-1 expression were significantly increased by 5-ALA/SFC treatment. The expression of toll-like receptors 2 and 4, NF-κB and inflammatory cytokines and ROS production in Kupffer cells were significantly decreased with 5-ALA/SFC treatment.
CONCLUSION
5-ALA/SFC significantly attenuates the injury level in the fatty liver after I/R injury.
背景
脂肪肝会增加严重急性缺血再灌注（I/R）损伤的风险，肝脂肪变性确实是移植脂肪肝后发生肝衰竭的主要危险因素。
材料与方法
对蛋氨酸和胆碱缺乏的高脂小鼠脂肪肝模型进行I/R损伤，同时给予或不给予5-氨基酮戊酸（5-ALA）/柠檬酸亚铁钠（SFC）治疗。评估肝酶水平、脂质过氧化和凋亡、炎性细胞因子和血红素加氧酶（HO）-1、肝脏中的一氧化碳（CO），以及分离的库普弗细胞中的活性氧（ROS）、炎性细胞因子和信号通路成员。
结果
I/R损伤后，丙氨酸转氨酶和天冬氨酸转氨酶水平、坏死区域数量、硫代巴比妥酸反应物质含量、TUNEL阳性细胞、浸润的巨噬细胞以及炎性细胞因子表达显著降低，而5-ALA/SFC治疗可使内源性CO浓度和HO-1表达显著增加。5-ALA/SFC治疗可使库普弗细胞中Toll样受体2和4、NF-κB和炎性细胞因子的表达以及ROS产生显著降低。
结论
5-ALA/SFC可显著减轻I/R损伤后脂肪肝的损伤程度。
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