CAJ | 학술논문

目的探讨输注受者同基因骨髓间充质干细胞对大鼠心脏移植后排斥反应的影响.方法以Wistar大鼠为供鼠,F344大鼠为受鼠建立异位心脏移植模型,以数字表法随机分为4组,每组各20对:急性排斥反应组(A组)受鼠仅行心脏移植;小剂量环孢素A组(B组)心脏移植受鼠输注小剂量环孢素A;骨髓间充质干细胞组(C组)心脏移植受鼠输注受鼠来源骨髓间充质干细胞;骨髓间充质干细胞联合小剂量环孢素A组(D组)受鼠输注受鼠来源骨髓间充质干细胞且输注小剂量环孢素A.观察各组受鼠移植心存活时间,检测血清细胞因子水平和脾脏组织叉状头转录因子3(Foxp3)基因表达量的变化,观察移植心组织的病理变化.结果 A组、B组、C组和D组移植心中位存活时间分别为7d、18d、16d和28 d,D组移植心存活时间长于其他组(P＜0.05);与其他各组相比较,D组术后白细胞介素2和γ干扰素水平明显降低(P＜0.05),白细胞介素6和白细胞介素10明显升高(P＜0.05).病理检查提示,D组移植心组织呈轻度排斥反应表现,B、C组呈中度排斥反应表现,A组呈急性重度排斥反应表现.A组Foxp3信使RNA表达量明显低于B、C、D组(P＜0.05),D组表达量也明显高于B、C组(P＜0.05),B、C组之间的差异无统计学意义(P＞0.05).结论同基因骨髓间充质干细胞输注联合小剂量环孢素A应用可减轻大鼠同种异体心脏移植排斥反应,并延长移植心脏的存活时间,其免疫调节作用的机制可能与Foxp3基因表达和细胞因子分泌有关.
목적 탐토수주수자동기인골수간충질간세포대대서심장이식후배척반응적영향.방법 이Wistar대서위공서,F344대서위수서건립이위심장이식모형,이수자표법수궤분위4조,매조각20대:급성배척반응조(A조)수서부행심장이식;소제량배포소A조(B조)심장이식수서수주소제량배포소A;골수간충질간세포조(C조)심장이식수서수주수서래원골수간충질간세포;골수간충질간세포연합소제량배포소A조(D조)수서수주수서래원골수간충질간세포차수주소제량배포소A.관찰각조수서이식심존활시간,검측혈청세포인자수평화비장조직차상두전록인자3(Foxp3)기인표체량적변화,관찰이식심조직적병리변화.결과 A조、B조、C조화D조이식심중위존활시간분별위7d、18d、16d화28 d,D조이식심존활시간장우기타조(P＜0.05);여기타각조상비교,D조술후백세포개소2화γ간우소수평명현강저(P＜0.05),백세포개소6화백세포개소10명현승고(P＜0.05).병리검사제시,D조이식심조직정경도배척반응표현,B、C조정중도배척반응표현,A조정급성중도배척반응표현.A조Foxp3신사RNA표체량명현저우B、C、D조(P＜0.05),D조표체량야명현고우B、C조(P＜0.05),B、C조지간적차이무통계학의의(P＞0.05).결론 동기인골수간충질간세포수주연합소제량배포소A응용가감경대서동충이체심장이식배척반응,병연장이식심장적존활시간,기면역조절작용적궤제가능여Foxp3기인표체화세포인자분비유관.
Objective To induce the immune tolerance of heart grafts with infusion of isogeneic bone marrow mesenchymal stem cells (BMSCs) in heart transplant rats.Method Donor Wistar rats and recipient F344 rats were randomly divided into 4 groups:acute rejection group (group A),Wistar rats as the donors and F344 rats as the recipients for heart transplantation; low dose cyclosporin A(CsA) group (group B),recipient F344 rats given low dose CsA; BMSCs group (group C),recipient F344 rats given isogeneic BMSCs; BMSC and low dose CsA group (group D),the recipient F344 rats given isogeneic BMSCs and low dose CsA.The serum cytokine levels were determined,and the donor heart pathological changes and survival were observed postoperatively.The relative level of Foxp3 mRNA expression in the spleen of the recipient F344 rats was also observed.Result The blood levels of interleukin-2 (IL-2) and interferon-γ(INF-γ) were significantly reduced,but IL-4 and IL-10 levels were increased (P＜0.05),and the survival time of donor heart was significantly prolonged in group D as compared with groups A,B and C (P＜0.05 for all).Heart pathological examination revealed a mild acute rejection in group D,moderate acute rejection in groups B and C group,and severe acute rejection in group A respectively.The expression of Foxp3 mRNA was significantly lower in group A than in groups B,C and D (P＜0.05 for all),and that in group D was significantly higher than in groups B and C (P＜0.05 for both),but there was no significant difference between between groups B and C (P＞0.05).Conclusion Intravenous administration of BMSCs can alleviate immunorejection in heterotopic rat heart transplantation.Low-dose CsA acts synergistically with BMSCs to significantly inhibit acute rejection after heart transplantation.The partial mechanisms involve the suppressive effect of BMSCs on the expression of Foxp3 mRNA and modulation on cytokine.