丹参对大鼠移植肝脏再灌注损伤的防护及肝细胞凋亡的影响

Effects of Radix salviae miltiorrhizae on reperfusion injury and hepatocyte apoptosis in donor liver after orthotopic liver transplantation in rats

目的研究含丹参冷灌注液对移植肝缺血再灌流损伤的防护及肝细胞凋亡的影响。方法将40只SD大鼠分为对照组、丹参组及假手术组,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,丹参组灌注保存液中加丹参注射液(60ml/L),对照组不加丹参。保存5h后置入受体。移植后6h处死大鼠取样,检测血清中AST、ALT及肝组织中氧自由基代谢相关指标丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平,采用TUNEL法检测移植术后肝细胞凋亡情况,光镜及透射电镜下观察移植肝脏组织形态学及超微结构的改变。结果移植肝再灌注后丹参组AST、ALT显著低于对照组。与对照组相比,丹参组肝细胞凋亡指数明显下降(P<0.01),肝组织中MDA含量较对照组降低(P<0.01),SOD、GSH-PX活性较对照组升高(P<0.01)。丹参组较对照组肝组织形态及超微结构上再灌注损害程度明显减轻。结论丹参可抑制冷保存再灌注导致的肝细胞凋亡,对原位肝移植肝脏的缺血-再灌注损伤有保护作用。

Objective To investigate the effect of Radix salviae miltiorrhizae as a cold reperfusion solution on donor liver ischemia-reperfusion injury and hepatocyte apoptosis in rat models of orthotopic liver transplantation. Methods Forty male SD rats were randomly divided into miltiorrhizae group, control group and sham operation group. For cold preservation of the graft, miltiorrhizae-containing Ringer＇s lactate solution was used as the reperfusion and preservation solution in the miltiorrhizae group, and only Ringer＇s lactate solution was used in the control group. All the grafts were preserved for 5 h before orthotopic transplantion. Six hours after graft reperfusion, the recipient rats were sacrificed, and the serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured, and the changes of malondialdehyde （MDA）, superoxide dismutase （SOD）, and glutathione peroxidase （GSH-Px） in the liver graft were observed. The hepatocyte apoptosis was detected using TUNEL, with the histopathological changes observed under light and electron microscopes. Results Serum ALT and AST levels were significantly lower in miltiorrhizae group than in the control group after graft reperfu.sion （P〈0.01）. Compared with the sham operation group, the apoptotic index and MDA levels in the graft was significantly decreased, while SOD and GSH-PX levels increased in miltiorrhizae group （P〈0.01）. Histopathological changes Were obviously milder in miltiorrhizae group than in the sham operation group. Conclusion Radix salviae miltiorrhizae can protect the hepatocytes from cold preservation and reperfusion-induced apoptosis and significantly alleviates ischemia-reperfusion injury in rat liver graft after orthotopic transplantation.