[血红素加氧酶对大鼠肝脏缺血再灌注损伤中细胞凋亡及凋亡相关基因的影响]

Wang Yang-Yang, Feng Zhi-Jie, Yue Yuan-Yuan, Song Mei, Song Wen-Jie

Department of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Zhonghua Gan Zang Bing Za Zhi. 2007 Dec;15(12):922-5.

OBJECTIVE

To use heme oxygenase (HO) inducer hemin and a HO inhibitor zinc protoporphyrin (ZnPP) to investigate the effect of HO on apoptosis and apoptosis genes in hepatic ischemia reperfusion (IR) injury in rats.

METHODS

Ninety-six Sprague-Dawley rats were randomly divided into four groups (24 rats in each): a sham-operation group, an ischemia-reperfusion (IR) group, a hemin-IR group and a ZnPP-IR group. Liver functions, liver histology and hepatocellular apoptosis rates were observed at 0, 1.5, 4 and 8 hours after reperfusion. Hepatocellular apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; expressions of Bcl-2 and caspase-3 were determined by Western blot.

RESULTS

Compared with the sham-operation group, the levels of ALT and AST were increased in the IR group. In the IR group the histological changes found in the livers were swelling of hepatocytes, narrowing of hepatic sinusoids, inflammatory cell infiltration and necrosis of hepatocytes in some areas of the livers. In the IR group rate of hepatocellular apoptosis was increased at 0, 1.5, 4 and 8 hours after reperfusion; expression of Bcl-2 was decreased and the expression of caspase-3 was increased. In the hemin-IR group, the levels of ALT and AST were lower, the pathological changes were milder and the rate of hepatocellular apoptosis was lower at 0, 1.5, 4 and 8 hours in comparison to those of the IR group. The expression of Bcl-2 was higher and the expression of caspase-3 was lower in the hemin-IR group in comparison to those of the IR group. The results in the ZnPP-IR group were just the opposite to those of the hemin-IR group.

CONCLUSION

HO might play a protective role in hepatic IR injury in rats, and this effect may be related to the inhibition of hepatocellular apoptosis.

目的

使用血红素加氧酶（HO）诱导剂血红素和HO抑制剂锌原卟啉（ZnPP），研究HO对大鼠肝脏缺血再灌注（IR）损伤中细胞凋亡及凋亡相关基因的影响。

方法

将96只Sprague-Dawley大鼠随机分为四组（每组24只）：假手术组、缺血再灌注（IR）组、血红素-IR组和ZnPP-IR组。再灌注后0、1.5、4和8小时观察肝功能、肝脏组织学及肝细胞凋亡率。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测肝细胞凋亡；采用蛋白质免疫印迹法检测Bcl-2和半胱天冬酶-3的表达。

结果

与假手术组相比，IR组丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平升高。IR组肝脏组织学变化表现为肝细胞肿胀、肝血窦变窄、炎性细胞浸润及部分区域肝细胞坏死。IR组再灌注后0、1.5、4和8小时肝细胞凋亡率升高；Bcl-2表达降低，半胱天冬酶-3表达升高。与IR组相比，血红素-IR组ALT和AST水平较低，病理变化较轻，再灌注后0、1.5、4和8小时肝细胞凋亡率较低。与IR组相比，血红素-IR组Bcl-2表达较高，半胱天冬酶-3表达较低。ZnPP-IR组结果与血红素-IR组相反。