摘要
目的观察低分子肝素对大鼠心脏移植物血管病（CAV）的作用及其机制。方法以SD大鼠为供者，Wistar大鼠为受者，进行异位（腹部）心脏移植。将受者分为3组，每组30只。CsA组自手术当天至术后第9天腹腔注射环孢素A（CsA）；实验组腹腔注射CsA（用法同CsA组），并从手术当天开始皮下注射低分子肝素，2mg·kg^-1·d^-1，直至处死；L-NAME组在给予低分子肝素的同时皮下注射左旋精氨酸甲酯（L_NAME），10nag·kg^-1·d^-1，其他用药同实验组。每组分别于术后30、60和90d各选取10只大鼠，测定血中NO及内皮素-1（ET-1）的浓度，切取移植心脏，镜下观察并进行CAV评分。结果随着时间的延长，各组的CAV评分逐渐升高，血NO浓度和ET-1浓度逐渐降低。实验组术后30、60和90d时的CAV评分分别为1．1±0．6、1．6±0．71和112．1±0．6，血ET-1浓度分别为（133±26）pg／ml、（106±16）pg／ml和（79±16）pg／ml，均明显低于CsA组和LNAME组（P〈0．05）；实验组术后30、60和90d时的血N0浓度分别为（171±22）μmol／L、（122±27）μmol／L和（92±17）μmol／L，均明显高于CsA组和L-NAME组（P〈0．05）。结论低分子肝素可以延缓心脏CAV的进展，其作用可能是通过增加NO的浓度和抑制ET-1的合成来实现的。
Objective To study the beneficial effects of LMWH on rat cardiac allograft vasculopathy and the underlying mechanisms. Methods Hearts from SD rats were heterotopically grafted into the abdomen of Wistar male recipients. Recipients were divided into 3 groups randomly as follows： control group, LMWH group and HL group with 30 rats in each group. Recipients in control group 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 LMWH and HL groups were treated with LMWH （2 mg·kg^-1·d^-1） till sacrificed. The NOS inhibitor, L-nitroarginine methyl ester （L-NAME） was also administered in HL group at a dosage of 10 mg·kg^-1·d^-1. At 30,60 and 90 days post operation, 10 recipients in each group were sacrificed for the harvest of blood sample and the graft. While recipients were sacrificed, hearts were harvested for cardiac allograft vasculopathy （CAV） score, and blood samples were collected for determination of nitric oxide （NO） and endothelin-1 （ET-1）. Results As the time passed,CAV score was increased,while NO and ET-1 were decreased gradually. CAV score and ET-1 in LMWH group were lower in all 3 time points. CAV scores were 1.1 ± 0. 6,1.6 ± 0. 7,2. 1 ± 0. 6,and ET-1 were （133 ± 26） pg/ml, （106 ± 16）pg/ml, （79 ± 16）pg/ml in 30,60 and 90 days, respectively. NO levels were （171 ±22） μmol/L, （122 ± 27） μmol/L, and （92 ± 17）μmol/L in 30,60 and 90 days, respectively. Compared with the other two groups, the development of CAV was attenuated in LMWH group at all 3 time points （P〈0. 05）. And recipients in LMWH group had higher NO and lower ET-1 levels （P〈 0. 05）. Conclusion LMWH could attenuate but not prevent the development of CAV, and the beneficial effect may be due to the increase of NO and decrease of ET-1. The beneficial effects of LMWH could be prevented by L-NAME.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2009年第3期141-143,共3页
Chinese Journal of Organ Transplantation
关键词
肝素
低分子量
心脏移植
冠状动脉狭窄
一氧化氮
大鼠
Heparin, low-molecular-weight
Heart transplantation
Coronary stenosis
Nitric oxide
Rats
