中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2013年
6期
366-369
,共4页
任雨%祁洪刚%张曙伟%金洁%朱音%朱炯%张英杰%高文波%楼江涌
任雨%祁洪剛%張曙偉%金潔%硃音%硃炯%張英傑%高文波%樓江湧
임우%기홍강%장서위%금길%주음%주형%장영걸%고문파%루강용
大鼠%主动脉,腹%移植%慢性移植物血管病%沙利度胺
大鼠%主動脈,腹%移植%慢性移植物血管病%沙利度胺
대서%주동맥,복%이식%만성이식물혈관병%사리도알
Rats%Aorta%Abdominal%Transplantation%Chronic graft vasculopathy%Thalidomide
目的 研究沙利度胺对慢性移植物血管病的缓解作用,并探讨其机制.方法 建立大鼠腹主动脉慢性移植物血管病模型.同系对照组的供、受者均为Brown-Norway大鼠(BN大鼠),术后每天以生理盐水灌胃；同种移植组均以BN大鼠为供者,Lewis大鼠为受者,术后每天以生理盐水灌胃,溶剂对照组术后每天以二甲基亚砜灌胃,高剂量组术后每天以沙利度胺200mg/kg灌胃,低剂量组术后每天以沙利度胺100mg/kg灌胃.术后8周,光镜下观察移植血管组织形态学变化；采用免疫组织化学法测定移植血管中白细胞介素9(IL-9)和转化生长因子β(TGF-β)表达情况；采用双抗体夹心酶联免疫吸附试验检测血清血小板衍生生长因子(PDGF)浓度.结果 同种对照组、溶剂对照组、高剂量组和低剂量组均呈现出典型的移植相关血管硬化,内膜明显增生,并呈同心圆增厚,同系对照组、同种对照组、溶剂对照组、高剂量组和低剂量组移植血管内膜厚度分别为(4.12±0.21)、(67.23±6.12)、(53.11±5.71)、(21.28±4.52)和(23.45±3.64)μm,高剂量组和低剂量组移植血管内膜厚度明显小于同种对照组和溶剂对照组(P＜0.05).同系对照组、同种对照组、溶剂对照组、高剂量组和低剂量组IL-9阳性细胞率分别为(12.54±4.56)％、(50.55±6.39)％、(45.26±2.32)％、(27.37±5.29)％和(29.11±3.20)％；TGF-β阳性细胞率分别为(18.12±6.21)％、(49.23±3.23)％、(40.61±4.13)％、(31.71±8.60)％和(29.35±6.85)％,高剂量组和低剂量组IL-9阳性细胞率和TGF-β阳性细胞率均明显低于同种对照组和溶剂对照组(P＜0.05).同系对照组、同种对照组、溶剂对照组、高剂量组和低剂量组血清中PDGF含量分别为0、(998±18)、(745±29)、(287±97)和(299±36)pg/ml,高剂量组和低剂量组血清PDGF含量均明显低于同种对照组和溶剂对照组(P＜0.05).结论 低剂量沙利度胺即可缓解慢性移植物血管病,这种作用可能与组织中TGF-β和IL-9表达下调,以及血清中PDGF浓度下降相关.
目的 研究沙利度胺對慢性移植物血管病的緩解作用,併探討其機製.方法 建立大鼠腹主動脈慢性移植物血管病模型.同繫對照組的供、受者均為Brown-Norway大鼠(BN大鼠),術後每天以生理鹽水灌胃；同種移植組均以BN大鼠為供者,Lewis大鼠為受者,術後每天以生理鹽水灌胃,溶劑對照組術後每天以二甲基亞砜灌胃,高劑量組術後每天以沙利度胺200mg/kg灌胃,低劑量組術後每天以沙利度胺100mg/kg灌胃.術後8週,光鏡下觀察移植血管組織形態學變化；採用免疫組織化學法測定移植血管中白細胞介素9(IL-9)和轉化生長因子β(TGF-β)錶達情況；採用雙抗體夾心酶聯免疫吸附試驗檢測血清血小闆衍生生長因子(PDGF)濃度.結果 同種對照組、溶劑對照組、高劑量組和低劑量組均呈現齣典型的移植相關血管硬化,內膜明顯增生,併呈同心圓增厚,同繫對照組、同種對照組、溶劑對照組、高劑量組和低劑量組移植血管內膜厚度分彆為(4.12±0.21)、(67.23±6.12)、(53.11±5.71)、(21.28±4.52)和(23.45±3.64)μm,高劑量組和低劑量組移植血管內膜厚度明顯小于同種對照組和溶劑對照組(P＜0.05).同繫對照組、同種對照組、溶劑對照組、高劑量組和低劑量組IL-9暘性細胞率分彆為(12.54±4.56)％、(50.55±6.39)％、(45.26±2.32)％、(27.37±5.29)％和(29.11±3.20)％；TGF-β暘性細胞率分彆為(18.12±6.21)％、(49.23±3.23)％、(40.61±4.13)％、(31.71±8.60)％和(29.35±6.85)％,高劑量組和低劑量組IL-9暘性細胞率和TGF-β暘性細胞率均明顯低于同種對照組和溶劑對照組(P＜0.05).同繫對照組、同種對照組、溶劑對照組、高劑量組和低劑量組血清中PDGF含量分彆為0、(998±18)、(745±29)、(287±97)和(299±36)pg/ml,高劑量組和低劑量組血清PDGF含量均明顯低于同種對照組和溶劑對照組(P＜0.05).結論 低劑量沙利度胺即可緩解慢性移植物血管病,這種作用可能與組織中TGF-β和IL-9錶達下調,以及血清中PDGF濃度下降相關.
목적 연구사리도알대만성이식물혈관병적완해작용,병탐토기궤제.방법 건립대서복주동맥만성이식물혈관병모형.동계대조조적공、수자균위Brown-Norway대서(BN대서),술후매천이생리염수관위；동충이식조균이BN대서위공자,Lewis대서위수자,술후매천이생리염수관위,용제대조조술후매천이이갑기아풍관위,고제량조술후매천이사리도알200mg/kg관위,저제량조술후매천이사리도알100mg/kg관위.술후8주,광경하관찰이식혈관조직형태학변화；채용면역조직화학법측정이식혈관중백세포개소9(IL-9)화전화생장인자β(TGF-β)표체정황；채용쌍항체협심매련면역흡부시험검측혈청혈소판연생생장인자(PDGF)농도.결과 동충대조조、용제대조조、고제량조화저제량조균정현출전형적이식상관혈관경화,내막명현증생,병정동심원증후,동계대조조、동충대조조、용제대조조、고제량조화저제량조이식혈관내막후도분별위(4.12±0.21)、(67.23±6.12)、(53.11±5.71)、(21.28±4.52)화(23.45±3.64)μm,고제량조화저제량조이식혈관내막후도명현소우동충대조조화용제대조조(P＜0.05).동계대조조、동충대조조、용제대조조、고제량조화저제량조IL-9양성세포솔분별위(12.54±4.56)％、(50.55±6.39)％、(45.26±2.32)％、(27.37±5.29)％화(29.11±3.20)％；TGF-β양성세포솔분별위(18.12±6.21)％、(49.23±3.23)％、(40.61±4.13)％、(31.71±8.60)％화(29.35±6.85)％,고제량조화저제량조IL-9양성세포솔화TGF-β양성세포솔균명현저우동충대조조화용제대조조(P＜0.05).동계대조조、동충대조조、용제대조조、고제량조화저제량조혈청중PDGF함량분별위0、(998±18)、(745±29)、(287±97)화(299±36)pg/ml,고제량조화저제량조혈청PDGF함량균명현저우동충대조조화용제대조조(P＜0.05).결론 저제량사리도알즉가완해만성이식물혈관병,저충작용가능여조직중TGF-β화IL-9표체하조,이급혈청중PDGF농도하강상관.
Objective To study the protective effects of thalidomide on the development of chronic graft vasculopathy and potential mechanisms.Method Rat abdominal aorta transplantation was performed on male Brown-Norway rats as donors and male Lewis rats as recipients.The recipients were divided into 5 groups:isograft control group (BN-BN) and allograft control group (BN-Lewis) were administrated with sodium chloride,solvents allograft control group (BN-Lewis) was administrated with dimethyl sulfoxide,low-dose experimental group (BN-Lewis) was administrated with low-dose thalidomide (100 mg/kg/day),and high dose experimental group (BN-Lewis) was administrated with high-dose thalidomide (200 mg/kg/day).All recipients were killed to harvest transplanted aorta at 8th week after transplantation.HE staining was used to observe the histological changes.The expression of IL-9 and TGF-β was detected by using immunohistochemical method.The serum concentration of PDGF was measured by using ABC-ELISA.Result The pathological changes in low-dose experimental group and high-dose experimental group were less severe than those in allograft control group and solvents allograft control group.The intimal thickness of transplantation blood vessel was (4.12 ± 0.21) μm in isograft control group,(67.23 ± 6.12) μm in allograft control group,(53.11 ± 5.71) μm in solvents allograft control group,(21.28 ± 4.52) μm in low-dose experimental group,and (23.45 ± 3.64) μm in high-dose experimental group.There were no obvious difference between the low-dose experimental group and high-dose experimental group.There were statistically significant differences between allograft control group or solvents allograft control group and low-dose experimental group or high-dose experimental group in the rate of cells positive for IL-9 and TGF-β,and the levels of serum PDGF.There was no statistically significant difference between low-dose experimental group and high-dose experimental group in the rate of cells positive for IL-9 and TGF β,and the levels of serum PDGF.Conclusion Low-dose thalidomide has protective effects on chronic allograft vasculopathy,which might be associated with the down-regulation of IL-9 and TGF-β,and the decrease in PDGF concentration.
