血红素氧合酶-1保护心力衰竭大鼠肠道结构屏障

Heme oxygenase-1 protects intestine structural barrier in heart failure rats

目的研究血红素氧合酶-1(HO-1)对心力衰竭大鼠肠道结构屏障的保护作用及其作用途径。方法通过冠状动脉结扎术造成心肌梗死建立心力衰竭大鼠模型(雄性,Wistar大鼠),分为MI+Copp(钴-原卟啉)组、MI(心肌梗死)模型组、MI+SnMP(锡中卟啉)组,相同数量(n=10)正常大鼠作为对照组(Control),分别腹腔注射Copp溶液、生理盐水、SnMP溶液、生理盐水。8周后在无菌术操作下取材肝、脾、肠系膜淋巴结,并匀浆细菌培养,计算细菌移位率;取小肠做HE染色观察病理。通过实时定量荧光PCR(Real-time PCR)测定小肠血红素氧合酶-1 RNA的表达,比色法测定小肠一氧化碳(CO)水平。结果同MI比较,MI+Copp明显升高小肠血红素氧合酶-1 RNA表达(P<0.01)及CO浓度(P<0.05),减轻小肠病理改变(P<0.05),并减少细菌移位率(P<0.01)、血浆内毒素含量[门静脉(61.790±21.038)pg/ml,下腔静脉(49.310±25.273)pg/ml,P<0.05]。而MI+SnMP对血红素氧合酶-1 RNA表达无明显影响(P>0.05),但明显降低小肠CO浓度(P<0.05),加重小肠病理改变(P<0.01),并升高细菌移位率(P<0.05)、血浆内毒素含量[门静脉(165.016±40.751)pg/ml,下腔静脉(141.249±40.772)pg/ml,P<0.01]。结论血红素氧合酶-1可明显减少心力衰竭大鼠细菌移位率及血浆内毒素含量,该作用可能与CO保护肠道屏障结构有关。

Objective To investigate the protective effect of heme oxygenase-1（HO-1） on intestine structural barrier in heart failure rats. Methods Heart failure rats model was built by myocardial infarction with coronary ligation method. These rats were randomized into 3 experimental groups（10 rats per group）： MI, MI＋Copp, and MI＋SnMP group receiving injection of saline, Cobalt protoporphyrin solution, Tin mesoporphyrin IX dichloride solution respectively,10 normal rats were set Control.8 weeks later, bacterial translocation incidence, endotoxine level in portal vein and inferior vena cava, expression of HO-1（heme oxygenase-1） and CO in intestine were determined. Results Compared with MI, MI＋Copp significantly reduced bacterial translocation incidence, endotoxine level with lower degree of morphology change and elevated concentration of HO-1 and CO, and this was abolished by SnMP. Conclusion MI＋ Copp can reduce bacterial translocation incidence and portal endotoxine level, which may be benefit to the protection of CO on intestine barrier.