中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2008年
3期
168-170
,共3页
张庆华%范明%田伟忱%姚志发%成明
張慶華%範明%田偉忱%姚誌髮%成明
장경화%범명%전위침%요지발%성명
肝素,低分子量%心脏移植%移植物排斥%一氧化氮合酶
肝素,低分子量%心髒移植%移植物排斥%一氧化氮閤酶
간소,저분자량%심장이식%이식물배척%일양화담합매
Heparin,low-molecular-weight%Heart transplantation%Graft rejection%Nitric-oxide synthase
目的 探讨低分子肝素对大鼠移植心脏急性和慢性排斥反应的影响及其机制.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.将受者随机分为急性排斥反应组(简称"急排组")和慢性排斥反应组(简称"慢排组").急排组中,15只于移植当天开始皮下注射低分子肝素200 μg穔g-1穌-1(小剂量者),直至移植心脏停搏;15只皮下注射低分子肝素2000 μg穔g-1穌-1(大剂量者),用药时间同前;以不给低分子肝素者作对照.慢排组所有受者均于移植当天至移植术后第9天腹腔注射环孢素A 5 mg·kg-1·d-1,其中10只还于移植当天至移植后第90天皮下注射低分子肝素2000 μg穔g-1穌-1,10只注射低分子肝素的同时再皮下注射左旋精氨酸甲酯(L-NAME)10mg·kg-1·d-1,以不给低分子肝素和L-NAME者作对照.移植后第5天,处死急排组部分受者,切取移植心脏,根据Stanford标准进行移植物排斥反应的病理学诊断和分级;剩余受者观察移植心脏存活时间.移植后第90天,测定慢排组受者的血NO浓度和移植心脏组织中诱生型NO合酶(iNOS)mRNA表达强度,并行心脏移植物血管病(CAV)评分.结果 急排组中,对照者、小剂量者和大剂量者的排斥反应等级评分分别为(4.20±0.45)分、(3.60±0.55)分和(2.40±0.55)分,移植心脏存活时问分别为(7.30±1.49)d、(8.20±1.47)d和(9.20±1.23)d,大剂量者的排斥反应等级评分明显低于对照者和小剂量者,移植心脏存活时间明显长于对照者和小剂量者(P＜0.05).慢排组中,仅给予低分子肝素者的血NO浓度和iNOS mRNA表达强度明显高于对照者和加用L-NAME者,而其CAV评分明显低于对照者和加用L-NAME者,差异均有统计学意义(P＜0.01).结论 低分子肝素可减轻急、慢性排斥反应程度,延长移植心脏存活时间;其抑制CAV的作用可能是通过上调iNOS mRNA表达水平,进而增加NO的释放来实现的.
目的 探討低分子肝素對大鼠移植心髒急性和慢性排斥反應的影響及其機製.方法 以SD大鼠為供者,Wistar大鼠為受者,進行異位(腹部)心髒移植.將受者隨機分為急性排斥反應組(簡稱"急排組")和慢性排斥反應組(簡稱"慢排組").急排組中,15隻于移植噹天開始皮下註射低分子肝素200 μg穔g-1穌-1(小劑量者),直至移植心髒停搏;15隻皮下註射低分子肝素2000 μg穔g-1穌-1(大劑量者),用藥時間同前;以不給低分子肝素者作對照.慢排組所有受者均于移植噹天至移植術後第9天腹腔註射環孢素A 5 mg·kg-1·d-1,其中10隻還于移植噹天至移植後第90天皮下註射低分子肝素2000 μg穔g-1穌-1,10隻註射低分子肝素的同時再皮下註射左鏇精氨痠甲酯(L-NAME)10mg·kg-1·d-1,以不給低分子肝素和L-NAME者作對照.移植後第5天,處死急排組部分受者,切取移植心髒,根據Stanford標準進行移植物排斥反應的病理學診斷和分級;剩餘受者觀察移植心髒存活時間.移植後第90天,測定慢排組受者的血NO濃度和移植心髒組織中誘生型NO閤酶(iNOS)mRNA錶達彊度,併行心髒移植物血管病(CAV)評分.結果 急排組中,對照者、小劑量者和大劑量者的排斥反應等級評分分彆為(4.20±0.45)分、(3.60±0.55)分和(2.40±0.55)分,移植心髒存活時問分彆為(7.30±1.49)d、(8.20±1.47)d和(9.20±1.23)d,大劑量者的排斥反應等級評分明顯低于對照者和小劑量者,移植心髒存活時間明顯長于對照者和小劑量者(P＜0.05).慢排組中,僅給予低分子肝素者的血NO濃度和iNOS mRNA錶達彊度明顯高于對照者和加用L-NAME者,而其CAV評分明顯低于對照者和加用L-NAME者,差異均有統計學意義(P＜0.01).結論 低分子肝素可減輕急、慢性排斥反應程度,延長移植心髒存活時間;其抑製CAV的作用可能是通過上調iNOS mRNA錶達水平,進而增加NO的釋放來實現的.
목적 탐토저분자간소대대서이식심장급성화만성배척반응적영향급기궤제.방법 이SD대서위공자,Wistar대서위수자,진행이위(복부)심장이식.장수자수궤분위급성배척반응조(간칭"급배조")화만성배척반응조(간칭"만배조").급배조중,15지우이식당천개시피하주사저분자간소200 μg황g-1소-1(소제량자),직지이식심장정박;15지피하주사저분자간소2000 μg황g-1소-1(대제량자),용약시간동전;이불급저분자간소자작대조.만배조소유수자균우이식당천지이식술후제9천복강주사배포소A 5 mg·kg-1·d-1,기중10지환우이식당천지이식후제90천피하주사저분자간소2000 μg황g-1소-1,10지주사저분자간소적동시재피하주사좌선정안산갑지(L-NAME)10mg·kg-1·d-1,이불급저분자간소화L-NAME자작대조.이식후제5천,처사급배조부분수자,절취이식심장,근거Stanford표준진행이식물배척반응적병이학진단화분급;잉여수자관찰이식심장존활시간.이식후제90천,측정만배조수자적혈NO농도화이식심장조직중유생형NO합매(iNOS)mRNA표체강도,병행심장이식물혈관병(CAV)평분.결과 급배조중,대조자、소제량자화대제량자적배척반응등급평분분별위(4.20±0.45)분、(3.60±0.55)분화(2.40±0.55)분,이식심장존활시문분별위(7.30±1.49)d、(8.20±1.47)d화(9.20±1.23)d,대제량자적배척반응등급평분명현저우대조자화소제량자,이식심장존활시간명현장우대조자화소제량자(P＜0.05).만배조중,부급여저분자간소자적혈NO농도화iNOS mRNA표체강도명현고우대조자화가용L-NAME자,이기CAV평분명현저우대조자화가용L-NAME자,차이균유통계학의의(P＜0.01).결론 저분자간소가감경급、만성배척반응정도,연장이식심장존활시간;기억제CAV적작용가능시통과상조iNOS mRNA표체수평,진이증가NO적석방래실현적.
Objective To observe the influence of LMWH on acute and chronic rejection of cardiac allograft.Methods Rat heterotopic heart transplantation model(abdomen)was established.Recipients were divided into acute(A for short)and chronic(C for short)groups randomly.In A group,dosage group)till death.Non-LMWH-treated recipients served as controls.All C group recipients were treated with cyclosporine A for 10 days from 0 to 9 postoperative day (POD) intraperitoneally.L-NAME served as controls.Five days post operation,some of recipients were sacrificed for the harvest of hearts,and grade of rejection was determined by Stanford grading system.Mean survival time was observed in acute groups while recipient hearts were harvested for CAV score,blood NO value and iNOS mRNA were detected in chronic groups 90 days post operation day.Results In A groups,rejection grades of control,lower dosage and higher dosage groups were 4.20±0.45,3.60±0.55 and 2.40±0.55,respectively.And the Mean survive time was 7.30±1.49,8.20±1.47 and 9.20±1.23 days,respectively.Significant differences were observed between higher dosage group and the other two groups in rejection grades and mean survive time(P＜0.05).CAV score,blood NO value and iNOS mRNA in situ hybridization had significant difference between LMWH-treated group and the other 2 groups(P＜0.01).Conclusion LMWH can prolong survive time of cardiac allograft and alleviate the development of CAV which is probably related with upregulation of iNOS mRNA and NO.
