CAJ | 학술논문

背景:肝移植后的排斥反应是威胁患者和移植物长期存活的主要原因.诱导受者产生特异性免疫耐受是解决排斥反应的理想措施.目的:探讨 RNAi RelB 树突状细胞预输注诱导大鼠肝移植特异性免疫耐受的可能性.方法:将近交系雄性清洁级 DA(RT1a)大鼠和近交系雄性 SPF 级 Lewis(RT11)大鼠分别作为供、受体,行原位肝移植手术.术前随机配对分为4组:①对照组,受体鼠移植前不做预输注.②治疗组:受体鼠移植前7 d 静脉输注供体大鼠 RNAi RelB 树突状细胞(5×106).③未成熟树突状细胞组:受体鼠移植前7 d 静脉输注供体大鼠未成熟树突状细胞(5×106).④成熟树突状细胞组:受体鼠移植前7 d 静脉输注供体大鼠成熟树突状细胞(5×106).结果与结论:与对照组、未成熟树突状细胞组以及成熟树突状细胞组相比,治疗组移植肝的平均生存时间显著延长.移植后第7天,治疗组天冬氨酸转氨酶,总胆红素水平低于对照组、成熟树突状细胞组、未成熟树突状细胞组(P <0.01),移植后第14天治疗组、未成熟树突状细胞组天冬氨酸转氨酶,总胆红素均有轻微下降,两组比较差异仍有显著性意义(P <0.01).移植后第7天,与治疗组比较,对照组、成熟树突状细胞组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平升高(P <0.01),而白细胞介素4、白细胞介素10下降(P <0.01);移植后第14天治疗组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平均有下降,白细胞介素4、白细胞介素10水平均有升高,两组比较差异仍有显著性意义(P <0.01).对照组、成熟树突状细胞组、未成熟树突状细胞组移植后第7天排斥活动指数为8.0-9.0.未成熟树突状细胞组第14天肝细胞、内皮细胞坏死及汇管区炎性细胞浸润进一步增多.治疗组移植后第7天排斥活动指数为6.0-8.0,第14天时排斥活动指数为4.0-5.0.结果提示RNAi RelB树突状细胞预输注可以减轻移植肝排斥程度,延长移植肝生存时间,这是通过间接途径实现的,其机制可能与T细胞的调节和无能有关. 揹景:肝移植後的排斥反應是威脅患者和移植物長期存活的主要原因.誘導受者產生特異性免疫耐受是解決排斥反應的理想措施.目的:探討 RNAi RelB 樹突狀細胞預輸註誘導大鼠肝移植特異性免疫耐受的可能性.方法:將近交繫雄性清潔級 DA(RT1a)大鼠和近交繫雄性 SPF 級 Lewis(RT11)大鼠分彆作為供、受體,行原位肝移植手術.術前隨機配對分為4組:①對照組,受體鼠移植前不做預輸註.②治療組:受體鼠移植前7 d 靜脈輸註供體大鼠 RNAi RelB 樹突狀細胞(5×106).③未成熟樹突狀細胞組:受體鼠移植前7 d 靜脈輸註供體大鼠未成熟樹突狀細胞(5×106).④成熟樹突狀細胞組:受體鼠移植前7 d 靜脈輸註供體大鼠成熟樹突狀細胞(5×106).結果與結論:與對照組、未成熟樹突狀細胞組以及成熟樹突狀細胞組相比,治療組移植肝的平均生存時間顯著延長.移植後第7天,治療組天鼕氨痠轉氨酶,總膽紅素水平低于對照組、成熟樹突狀細胞組、未成熟樹突狀細胞組(P <0.01),移植後第14天治療組、未成熟樹突狀細胞組天鼕氨痠轉氨酶,總膽紅素均有輕微下降,兩組比較差異仍有顯著性意義(P <0.01).移植後第7天,與治療組比較,對照組、成熟樹突狀細胞組、未成熟樹突狀細胞組γ-榦擾素、白細胞介素2水平升高(P <0.01),而白細胞介素4、白細胞介素10下降(P <0.01);移植後第14天治療組、未成熟樹突狀細胞組γ-榦擾素、白細胞介素2水平均有下降,白細胞介素4、白細胞介素10水平均有升高,兩組比較差異仍有顯著性意義(P <0.01).對照組、成熟樹突狀細胞組、未成熟樹突狀細胞組移植後第7天排斥活動指數為8.0-9.0.未成熟樹突狀細胞組第14天肝細胞、內皮細胞壞死及彙管區炎性細胞浸潤進一步增多.治療組移植後第7天排斥活動指數為6.0-8.0,第14天時排斥活動指數為4.0-5.0.結果提示RNAi RelB樹突狀細胞預輸註可以減輕移植肝排斥程度,延長移植肝生存時間,這是通過間接途徑實現的,其機製可能與T細胞的調節和無能有關.
배경:간이식후적배척반응시위협환자화이식물장기존활적주요원인.유도수자산생특이성면역내수시해결배척반응적이상조시.목적:탐토 RNAi RelB 수돌상세포예수주유도대서간이식특이성면역내수적가능성.방법:장근교계웅성청길급 DA(RT1a)대서화근교계웅성 SPF 급 Lewis(RT11)대서분별작위공、수체,행원위간이식수술.술전수궤배대분위4조:①대조조,수체서이식전불주예수주.②치료조:수체서이식전7 d 정맥수주공체대서 RNAi RelB 수돌상세포(5×106).③미성숙수돌상세포조:수체서이식전7 d 정맥수주공체대서미성숙수돌상세포(5×106).④성숙수돌상세포조:수체서이식전7 d 정맥수주공체대서성숙수돌상세포(5×106).결과여결론:여대조조、미성숙수돌상세포조이급성숙수돌상세포조상비,치료조이식간적평균생존시간현저연장.이식후제7천,치료조천동안산전안매,총담홍소수평저우대조조、성숙수돌상세포조、미성숙수돌상세포조(P <0.01),이식후제14천치료조、미성숙수돌상세포조천동안산전안매,총담홍소균유경미하강,량조비교차이잉유현저성의의(P <0.01).이식후제7천,여치료조비교,대조조、성숙수돌상세포조、미성숙수돌상세포조γ-간우소、백세포개소2수평승고(P <0.01),이백세포개소4、백세포개소10하강(P <0.01);이식후제14천치료조、미성숙수돌상세포조γ-간우소、백세포개소2수평균유하강,백세포개소4、백세포개소10수평균유승고,량조비교차이잉유현저성의의(P <0.01).대조조、성숙수돌상세포조、미성숙수돌상세포조이식후제7천배척활동지수위8.0-9.0.미성숙수돌상세포조제14천간세포、내피세포배사급회관구염성세포침윤진일보증다.치료조이식후제7천배척활동지수위6.0-8.0,제14천시배척활동지수위4.0-5.0.결과제시RNAi RelB수돌상세포예수주가이감경이식간배척정도,연장이식간생존시간,저시통과간접도경실현적,기궤제가능여T세포적조절화무능유관.
BACKGROUND: Homograft rejection is the most important factor that limits the survival of recipients and donor organs fter liver transplantation. Induced specific immune tolerance is a most satisfactory method to release rejection after transplantation. OBJECTIVE: To explore the possibility of the specific immune tolerance induced by RNA interference RelB dendritic cel s pre-infusion after liver transplantation in rats. METHODS: A stable rat model of acute rejection was established by al ograft liver transplantation from DA (RT1a) rats to Lewis (RT11) rats. Before transplantation, the donor and recipient rats were paired and randomly divided into four groups:(1)Control group: the recipient rats were not injected before liver transplantation. (2)RNA interference RelB treatment group: the recipient rats were pre-injected with RNA interference RelB dendritic cel s from donor (5×106) via veins at the 7 days before transplantation. (3)Immature dendritic cel s group: the recipient rats were pre-injected with immature dendritic cel s (5×106) from donor via veins at the 7 days before transplantation. (4)Mature dendritic cel s group: the recipient rats were pre-injected with mature dendritic cel s (5×106) from donor via veins at the 7 days before transplantation. RESULTS AND CONCLUSION: Compared with control group, immature dendritic cel s group and mature dendritic cel s group, the average survival time of graft renal in RNA interference RelB treatment group prolonged significantly (P < 0.01). The content of aspartate aminotransferase and total bilirubin in RNA interference RelB treatment group at 7 days after transplantation were significantly lower that those in the control group, immature dendritic cel s group and mature dendritic cel s group (P < 0.01), while the content of aspartate aminotransferase and total bilirubin at 14 days after transplantation in RNA interference RelB treatment group and immature dendritic cel s group were slightly decreased, and there was significant difference between two groups (P < 0.01). At 7 days after transplantation, compared with RNA interference RelB treatment group, the contents of interferon-γ and interleukin-2 were increased in the control group, immature dendritic cel s group and mature dendritic cel s group (P < 0.01), while the contents of interleukin-4 and interleukin-10 were decreased (P < 0.01); at 14 days after transplantation, the contents of interferon-γ and interleukin-2 were decreased and the contents of interleukin-4 and interleukin-10 were increased in RNA interference RelB treatment group and immature dendritic cel s group, and there was significant difference between two groups (P < 0.01). At 7 days after transplantation, the rejection active index in the control group, immature dendritic cel s group and mature dendritic cel s group was 8.0-9.0. At 14 days after transplantation, more necrosis of hepatocytes and endotheliocyte and inflammatory cel s imbibition in header zone were observed in immature dendritic cel s group. The rejection active index in RNA interference RelB treatment group at 7 days after transplantation was 6.0-8.0, and rejection active index was 4.0-5.0 at 14 days after transplantation. Pre-injection of RNA interference RelB dendritic cel s may contribute to reduce the degree of graft rejection and prolong the survival time of grafted liver, which related to the regulation and immune-incompetent of T cel s.