缺血-再灌注损伤大鼠肝组织HIF-1α和VEGF的表达及其意义

doi:10.3877/cma.j.issn.2095-3232.2015.05.014

目的

探讨缺血-再灌注损伤（IRI）大鼠肝组织缺氧诱导因子（HIF）-1α和VEGF的表达及其意义。

方法

按随机数字表法将16只SD大鼠分为IRI组和假手术组（Sham组），每组8只。IRI组用无损伤血管夹夹闭大鼠门静脉和肝动脉的分支，缺血45 min，再恢复灌注6 h；Sham组仅暴露肝门，不阻断肝血流。观察两组大鼠肝组织形态学的改变，检测血清ALT、AST水平，测定肝组织HIF-1α、VEGF的蛋白含量。两组数据比较采用t检验。

结果

光镜下可见IRI组大鼠肝细胞肿胀，空泡变性，炎症细胞浸润，肝窦扩张，肝细胞索排列紊乱，点状坏死；Sham组肝组织形态正常。IRI组血清ALT、AST分别为（1 007±130）、（1 307±72）U/L，较Sham组的（59±4）、（81±3）U/L明显升高（t=20.700，48.448；P<0.05）。IRI组肝组织HIF-1α、VEGF蛋白相对表达量分别为1.77±0.10、1.86±0.05，较Sham组的0.60±0.22、0.83±0.06明显增加（t=13.623，35.563；P<0.05）。

结论

IRI早期大鼠肝组织HIF-1α和VEGF表达明显增加，可能起到减轻机体IRI的作用。

关键词: 肝, 再灌注损伤, 缺氧诱导因子1，α亚基, 血管内皮生长因子类, 大鼠

Objective

To investigate the expression and significance of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in liver tissues after ischemia-reperfusion injury (IRI) in rats.

Methods

Sixteen Sprague-Dawley (SD) rats were randomized into the IRI group and the Sham group according to the random number table, 8 rats in each group. The portal vein and branches of hepatic artery of the rats in the IRI group were clamped with the atraumatic vascular clamp. After 45 min of ischemia, reperfusion was performed for 6 h. The porta hepatis of rats in the Sham group was exposed and the hepatic blood flow was not occluded. The morphological changes of the liver tissues in two groups were observed. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested and the contents of HIF-1α and VEGF in liver tissues were determined. Data comparison between two groups was conducted using t test.

Results

Under light microscope, swelling, vacuolar degeneration of the liver cells, inflammatory cell infiltration, hepatic sinusoidal dilatation, disorganized hepatic cords and spotty necrosis were observed in the IRI group. The histomorphology of liver tissues in the Sham group was normal. The serum ALT and AST in the IRI group was respectively (1 007±130) and (1 307±72) U/L, which were significantly higher than (59±4) and (81±3) U/L in the Sham group (t=20.700, 48.448; P<0.05). The relative expression of HIF-1α and VEGF in liver tissues of IRI group was 1.77±0.10 and 1.86±0.05 respectively, which were significantly higher than 0.60±0.22 and 0.83±0.06 in the Sham group (t=13.623, 35.563; P<0.05).

Conclusion

The expression of HIF-1α and VEGF in liver tissues increase significantly during early IRI, which may play a role in reducing the IRI of organism.

Key words: Liver, Reperfusion injury, Hypoxia-inducible factor 1, alpha subunit, Vascular endothelial growth factors, Rats

图1 IRI组和Sham组大鼠肝组织切片图（HE ×100）

表1 两组大鼠血清ALT、AST水平和肝组织HIF-1α、VEGF蛋白相对表达量比较（±s）

组别	鼠数（只）	ALT (U/L)	AST (U/L)	HIF-1α	VEGF
IRI组	8	1 007±130	1 307±72	1.77±0.10	1.86±0.05
Sham组	8	59±4	81±3	0.60±0.22	0.83±0.06
t值	?	20.700	48.448	13.623	35.563
P值	?	<0.05	<0.05	<0.05	<0.05

表1 两组大鼠血清ALT、AST水平和肝组织HIF-1α、VEGF蛋白相对表达量比较（±s）

组别	鼠数（只）	ALT (U/L)	AST (U/L)	HIF-1α	VEGF
IRI组	8	1 007±130	1 307±72	1.77±0.10	1.86±0.05
Sham组	8	59±4	81±3	0.60±0.22	0.83±0.06
t值	?	20.700	48.448	13.623	35.563
P值	?	<0.05	<0.05	<0.05	<0.05

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Expression and significance of HIF-1α and VEGF in liver tissues after ischemia-reperfusion injury in rats

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Expression and significance of HIF-1α and VEGF in liver tissues after ischemia-reperfusion injury in rats