丹参对原位肝移植大鼠供肝冷保存再灌注损伤的保护作用

Effects of radix salvia miltiorrhiz on protecting donor liver against cold preservation and reperfusion injury during orthotopic liver transplantation in rats

目的:研究表明,丹参对心、脑、肝等重要器官的缺血再灌注损伤有保护作用。制备大鼠异体原位肝移植模型,验证丹参对大鼠肝移植缺血再灌流损伤的保护作用。方法:实验于2006-10/2007-08在南方医院中心实验室及动物实验中心完成,动物实验方法符合动物伦理学要求。①实验材料及分组:选用SD大鼠40只,按随机数字表法分为假手术组、模型对照组和丹参注射液组,假手术组8只,模型对照组、丹参注射液组各8对(供体与受体)。②实验方法:建立原位肝移植模型,在供肝灌注冷保存时,以4℃乳酸林格氏液为基液,丹参注射液组灌注保存液中加60mL/L丹参注射液;模型对照组不加丹参。③实验评估:移植术后6h处死各组大鼠取样,检测血清谷草转氨酶、谷丙转氨酶及乳酸脱氢酶活性;测定肝组织中丙二醛含量及超氧化物歧化酶、谷胱甘肽过氧化物酶活性,并对比观察移植肝病理形态学改变。结果:模型对照组和丹参注射液组16只受体大鼠及假手术组8只大鼠全部进入结果分析,无脱失。①丹参注射液组和模型对照组移植肝再灌注后血清谷丙转氨酶、谷草转氨酶及乳酸脱氢酶活性均高于假手术组(P<0.01);丹参注射液组低于模型对照组(P<0.01)。②丹参注射液组肝组织中丙二醛含量较模型对照组明显下降(P<0.01),超氧化物歧化酶和谷胱甘肽过氧化物酶的活性则明显升高(P<0.01)。③丹参注射液组较模型对照组肝组织肝细胞坏死程度减轻,炎性细胞浸润减少,肝组织再灌注损害程度减轻。结论:丹参对原位肝移植肝脏的缺血再灌注损伤有保护作用,从而减轻氧自由基及脂质过氧化,保护细胞膜,改善肝功能。

AIM：Studies reveal that radix salvia miltiorrhiz can protect critical organs such as heart, brain and liver, etc. from ischemia/reperfusion injury. This study established orthotopic liver transplantation model in rats and investigated the protective effect of radix salvia miltiorrhiz on the ischemia/reperfusion injury. METHODS： The experiment was carried out in the Central Laboratory and Animal Experimental Center of Nanfang Hospital between October 2006 and August 2007. And the experimental procedures were in accordance with the ethical standard of animals.①Forty SD rats were randomly divided into radix salvia miltiorrhiz experimental group （n=16）, model control group （n=16） and pseudo-treatment group （n=8）.②Rat orthotopic liver transplantation model was established. Perfusion and preserving solution at 4 ℃ were miltiorrhiz Ringer＇s lactate solution （60 mL/L） in the miltiorrhiz experimental group and Ringer＇s lactate solution without miltiorrhiz in the model control group.③Six hours after reperfusion, the recipients were sacrificed, then serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and lactate dehydrogenase （LDH） activities were measured. The changes of malondialdehyde （MDA）, superoxide dismutase （SOD） and glutathion peroxidase （GSH-Px） in the liver tissues were observed. The histopathological changes were also compared. RESULTS： All of 40 rats were involved in the result analysis without loss.①Serum ALT, AST, LDH levels in the miltiorrhiz experimental group and model control group were higher than those in the pseudo-treatment group after the grafts reperfusion （P〈0.01）, and these levels were lower in the miltiorrhiz experimental group than in the model control group （P〈0.01）.②Compared with model control group, the liver MDA levels were significantly lower （P〈0.01）, while SOD and GSH-PX levels were significantly higher in the miltiorrhiz experimental group （P〈0.01）.③Compared with model control group, the hepatic cell necrosis lessened, inflammatory cell infiltration decreased and the liver tissue reperfusion injury relieved in the miltiorrhiz experimental group. CONCLUSION： Radix salvia miltiorrhiz can decrease oxygen-derived free radical and lipid peroxidation, protect cell membrane, and improve hepatic function by the protective effect on the ischemia/reperfusion injury in orthotopic liver transplantation.