阿霉素诱导亚铁血红素氧化酶-1在大鼠肝、脾和肾脏组织的表达及其对肝功能的影响

目的：观察阿霉素诱导亚铁血红素氧化酶-1（HO-1）在大鼠肝、脾和肾脏组织的表达及对肝功能的影响。方法：雄性Wistar大鼠随机分为空白对照组、小剂量阿霉素组(1 mg•kg^-1) 和大剂量阿霉素组(10 mg•kg^-1)，分别于给药后6、12、18、24和48 h切取阿霉素组与对照组部分肝脏用蛋白电泳法检测HO-1表达，切取注药后48 h阿霉素组和对照组部分肝、脾和肾行HO-1免疫组化染色，同时检测三组大鼠肝功能、血清ET-1和TNF-α。结果：蛋白电泳检测显示HO-1蛋白在正常肝脏内的表达阴性；给药后6 h两组均可检测出HO-1的表达，24 h达到高峰，48 h HO-1表达已明显减弱。免疫组化染色显示，注射阿霉素48 h,肝、脾和肾仍可见大量HO-1染色阳性细胞；对照组肝脏无染色阳性细胞，脾肾可见少量染色阳性细胞。肝功能指标、血清TNF-α和ET-1对照组与小剂量阿霉素组差异无显著性(P>0.05)，大剂量阿霉素组上述指标明显高于对照组和小剂量阿霉素组(P<0.05)。结论：阿霉素可诱导肝脏、脾脏和肾脏HO-1表达，小剂量阿霉素对大鼠肝脏未造成明显损害。

Expression of heme oxygenase-1 induced by doxorubicin in liver,spleen,and kidney and effect of doxorubicin on liver function

Objective To study the expression of heme oxygenase 1 (HO 1) induced by doxorubicin in liver,spleen, and kidney and the effect of doxorubicin on liver function. Methods Male Wistar rats were randomly divided into control, low dose (1 mg·kg -1 ) and high dose(10 mg·kg -1 ) group. The expressions of HO 1 in liver were detected by Western blot in the two doxorubicin groups 6,12,18,24, and 48 hours later after the injection. The expressions of HO 1 in liver,spleen and kidney were also detected by immunohistochemistry 48 hours later after the injection and at the same time the indicator of liver function test, serum TNF α and ET 1 were also determined in the three groups. Results The expression of HO 1 in liver could be detected by Western blot 6 hours later after the injection in the two doxorubicin groups and the expression increased continuously until 24 hours later. The expression of HO 1 was also detected in liver,spleen and kidney by immunohistochemistry 48 hours later after the injection of doxorubicin. The indicator of liver function test,serum TNF α and ET 1 were much higher in the high dose doxorubicin group than those in the control group and low dose doxorubicin group ( P <0 05), there was no significant difference between the control and low dose doxorubicin groups ( P >0 05). Conclusion Doxorubicin can induce the expression of HO 1 in liver,spleen and kidney, low dose doxorubicin may do no harm to liver.