穿心莲成分API_(0134)对大鼠心脏移植物血管病作用的研究

Study of the effects of API_(0134) on rat cardiac allograft vasculopathy

目的研究穿心莲成分API0134对大鼠心脏移植物血管病(cardiac allograft vasculopathy,CAV)的作用及其机制。方法采用大鼠异位心脏移植模型,对照组:n=20,自移植后当天至术后第9天腹腔注射环孢素A(CsA);实验组:n=20,腹腔注射CsA(用法同对照组),并从手术当天腹腔注射API0134,50mg/(kg.d)直至处死。每组分别于术后2个月和3个月各取10只大鼠,测定各组的CAV评分、血浆超氧化物歧化酶(SOD)和丙二醛(MDA)含量。结果移植后2个月和3个月,实验组心脏移植物血管病评分显著低于对照组,分别为1.2±0.2和2.5±0.4(P<0.05),1.7±0.5和2.9±0.7(P<0.05)。实验组血浆SOD均显著高于对照组,分别为(157.85±14.53)U/mL和(120.72±14.40)U/mL(P<0.05),(154.10±15.18)U/mL和(128.14±15.78)U/mL(P<0.05);实验组血浆MDA均显著低于对照组,分别为(4.66±0.82)nmol/mL和(10.52±1.81)nmol/mL(P<0.05),(4.80±0.21)nmol/mL和(11.13±1.26)nmol/mL(P<0.05)。结论 API0134可以延缓CAV的进展,其机制可能是通过减轻氧化应激对冠状血管内皮的损害来实现的。

Objective To study the beneficial effects of API0134 on rat cardiac allograft vasculopathy（CAV） and its possible mechanisms.Methods The rat cardiac allograft model was used.Recipients in control group（n=20） were treated with cyclosporine A（CsA） for 10 days from 0 to 9 postoperative days to avoid acute rejection and allow for the development of chronic rejection.In addition,recipients in experimental group（n=20） were treated with API0134（50mg·kg-1·d-1） till sacrificed.CAV score was evaluated,plasma superoxide dismutase（SOD） and malondialdehyde（MDA） were measured at 2 and 3 months postoperation.Results CAV score was significantly lower in experimental group than that in control group both at 2nd month（1.2±0.2 vs 2.5±0.4,P0.05） and 3rd month（1.7±0.5 vs 2.9±0.7,P0.05）.The plasma SOD was significantly higher in experimental group than that in control group both at 2nd month（157.85±14.53 U/mL vs 120.72±14.40 U/mL,P0.05） and 3rd month（154.10±15.18 U/mL vs 128.14±15.78 U/mL,P0.05） after transplantation.The plasma MDA was significantly lower in experimental group than that in control group both at 2nd month（4.66±0.82 nmol/mL vs 10.52±1.81 nmol/mL,P0.05） and 3rd month（4.80±0.21 nmol/mL vs 11.13±1.26nmol/mL,P0.05） after transplantation.The cardiac allografts in experimental group showed minimal intimal proliferation,the endothelium and internal elastic lamina remained almost intact,and reduced smooth muscle cell proliferation.Conclusion API0134 could attenuate but not prevent the development of CAV,and the mechanism may be due to reduced damage of vascular endothelium by oxidative stress after heart transplantation.