肌肽抗全身性缺血/再灌注损伤作用的研究

Protective effect of carnosine on general ischemia-reperfusion injury in rats

目的通过失血性休克大鼠血液回输后造成的全身性缺血/再灌注损伤(IRI)模型,研究肌肽对全身性IRI的保护作用。方法36只Wistar大鼠随机分成假手术组、休克损伤组、再灌损伤组和肌肽治疗组。制作大鼠IRI模型大鼠失血至40mmHg→维持20min→放置1h→全血回输→维持3h→处死。假手术组大鼠手术后处死;休克损伤组大鼠输血前处死;再灌损伤组和三个肌肽治疗组输血前分别静脉推注生理盐水或90mg/kg肌肽,大鼠放置3h后处死。大鼠处死后取血浆检测乳酸脱氢酶(LDH)活性及丙二醛(MDA)浓度;取肝、脑、肺、心、肾组织制作石蜡切片,观察组织病理改变,取肝组织制作肝细胞悬液检测肝细胞凋亡率。结果与休克损伤组相比,再灌损伤组血浆LDH活性及MDA浓度显著升高(P<0.01,P<0.05)、组织病理损伤明显加重。与再灌损伤组相比,肌肽治疗组血浆LDH活性及MDA浓度显著降低(P<0.01);肝、脑、肺、心、肾组织切片病理损伤明显减轻;肝细胞凋亡率显著降低(P<0.05)。结论肌肽对全身性IRI具有保护作用。

Objective To investigate the protective effects of carnosine in a Wistar rat model of ischemia - reperfusion injury. Methods Thirty - six male Wistar rats were randomly divided into sham operation group, shock group, mock treated IRI group and carnosin treated IRI group. Animal ischemia was achieved by hemorrhage and reperfusion injury was achieved by infusion of the bled blood. Rats of the sham operation group and shock group were sacrificed after operation and hemorrhage for 1 hour respectively. The mock treated IRI group and carnosine treated IRI group received 0. 9% sodium chloride solution and carnosine （90 mg/kg） through femoral vein before reperfusion respectively. The total bled blood was reinfused into the animals in 10 minutes and the rats were sacrificed 3 hours later. Blood samples were analyzed for serum lactate dehydrogenase （ LDH ） activity and malondialdehyde （ MDA ） concentration. And liver, brain, lung, heart and kidney samples were taken for the examination of histopathology. The apoptosis rate of hepatic cells of mock treated IRI group and optimal therapeutic dosage treated IRI group was measured and compared. Results Compared with those in shock group, the serum LDH and MDA levels increased significantly in mock treated IRI group （ P 〈 0. 01 ,P 〈 0. 05 ） and histopathological examination revealed severe lesions. Compared with those in mock treated IRI group the serum LDH and MDA levels and apoptosis rate of hepatic cell in the carnosine treated group decreased significantly（ P 〈 0. 01, P 〈 0. 05 ）. Conclusion The present studies reveal that carnosine administration is useful in protection of the animals subjected to general IRI.