Research Laboratory of Biochemistry, Basic Medical Institute, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
World J Gastroenterol. 2010 Nov 21;16(43):5424-34. doi: 10.3748/wjg.v16.i43.5424.
To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury.
A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously.
Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60'R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047).
Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.
评价瘦素在肝缺血/再灌注损伤时的内在紊乱中的作用。
建立 70%肝缺血/再灌注损伤大鼠模型，分为假手术（Sham）组、60 分钟缺血/60 分钟再灌注（I60'R60'）组、I60'R150'组、I60'R240'组和 I60'R360'组。采用自制放射免疫法检测血清瘦素；相关试剂盒检测血清葡萄糖、总抗氧化能力、髓过氧化物酶、丙氨酸氨基转移酶和二胺氧化酶；通过苏木精-伊红染色和免疫组织化学检测肺、肝和十二指肠组织中瘦素的组织学改变和蛋白水平。同时分析瘦素与其他变量或组织损伤分级之间的 Spearman 秩相关关系。
I60'R360'组血清瘦素明显高于 Sham 组和 I60'R240'组（均 P < 0.05），I60'R360'组血清葡萄糖高于 Sham 组和 I60'R150'组（均 P < 0.05），I60'R240'组和 I60'R360'组血清总抗氧化能力高于 Sham 组和 I60'R150'组（均 P < 0.01）。I60'R240'组和 I60'R360'组血清髓过氧化物酶低于 I60'R150'组（均 P < 0.05），四再灌注组血清丙氨酸氨基转移酶均高于 Sham 组（均 P < 0.05），而 I60'R360'组血清二胺氧化酶低于 I60'R60'组（P < 0.05）。在损伤早期，肺、肝和十二指肠的组织损伤更严重，但在后期逐渐减轻。四再灌注组肺组织瘦素蛋白水平均明显低于 Sham 组（均 P < 0.01），按 I60'R150'、I60'R60'、I60'R360'和 I60'R240'的顺序降低；I60'R60'组和 I60'R240'组肝组织瘦素水平高于 Sham 组（均 P < 0.01），而 I60'R240'组和 I60'R360'组肝组织瘦素水平低于 I60'R60'组（均 P < 0.01）；I60'R240'组和 I60'R360'组十二指肠组织瘦素水平高于 Sham、I60'R60'和 I60'R150'组（均 P < 0.01），而 I60'R150'组低于 I60'R60'组（P < 0.05）。血清瘦素与丙氨酸氨基转移酶呈显著正相关（ρ = 0.344，P = 0.021），肺组织瘦素蛋白水平与损伤评分呈显著负相关（ρ = -0.313，P = 0.036），肝组织瘦素蛋白水平与损伤评分呈显著正相关（ρ = 0.297，P = 0.047）。
内源性瘦素在肝缺血/再灌注损伤中波动，对内在紊乱具有康复作用，是支持治疗的潜在靶点。
