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微囊化异种肝细胞移植对药物性肝衰的治疗作用及免疫隔离机制的初步研究

Pilot study of treatment and immunity isolation mechanism of rat toxic hepatic failure by using transplanted microencapsulated xenogeneic hepatocyte

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【作者】 何震宇高蓓朱泰来陈永田张峰杨春张萍

【Author】 HE Zhen-yu, GAO Bei, ZHU Tai-lai, et al (The second Affiliated Hospital of Nanjing Medical University,Jiangsu Nanjing 210011, China)$$$$

【机构】 南京医科大学第二附属医院普外科南京医科大学第一附属医院移植中心南京医科大学第二附属医院普外科 江苏南京210011江苏南京210011江苏南京210011

【摘要】 目的 :探讨微囊化异种肝细胞脾内移植对药物性肝衰大鼠的治疗作用 ;测定受体存活率、肝功能的变化及CD4 ,CD8的变化。方法 :海藻酸钠体外包裹经胶原酶技术制备的异种 (豚鼠 )肝细胞为供体 ,SD大鼠为受体 ,D -氨基半乳糖 (19.5ml/kg)腹腔内一次性注射 ,制作肝衰模型。 4 8h后将微囊化的游离豚鼠肝细胞 (1.5× 10 7)移植于大鼠脾脏内。以豚鼠裸肝细胞 (1.5× 10 7)移植及生理盐水1.2ml脾脏注射为对照。移植后 14d观察存活率、肝功能及肝脏病理情况 ,免疫组化ABC法测定CD4 ,CD8的变化。结果 :微囊化肝细胞移植组存活率 80 % ,明显高于生理盐水组 (2 5 % )和裸肝细胞移植组(70 % )。 (P <0 .0 1 V P <0 .0 5 )。微囊肝细胞移植组 14d总胆红素 (7.99± 0 .5 8mg/L)和ALT(5 5±6 .7u) ,明显低于生理盐水组 (9.6 3± 0 .83mg/LV 91± 8.0u)和裸肝细胞组 (8.9± 0 .6 6mg/LV 74± 7.1u)(P <0 .0 5VP <0 .0 1)。移植后 12h ,72h ,14d分别测定受体脾脏CD4 ,CD8淋巴细胞 ,微囊化肝细胞组72h ,14d呈阳性。裸肝细胞组均呈阳性。结论 :大鼠药物性肝衰微囊化肝细胞脾内移植后维持存活率14d ,细胞免疫参与排斥反应 ,肝细胞微囊化处理可延迟细胞免疫的发生时间。

【Abstract】 Objective: To investigate the change of CD4 ,CD8, survival rate and hepatic function of xenogeneic encapsulated hepatocytes intraspleen transplantation (XHT) in the treatment of toxic hepatic failure (THF) in SD rat. Methods: Twenty SD rats received intraspleen grafts of 1.5×10 7guinea pig encapsulation hepatocytes by alginate-barium at 48h after D-glactosamine (D-GI) introperitonear injection(19.5mg/kg).Guinea pig free hepatocytes transplantation(1.5×10 7) or 1.2ml injection (FHT n=20 ) and N.S injection 1.2ml (N.S n=20 ) was belonged to control groups. The results of CD4, CD8, survival rate and hepatic function were carried out at 14 days after transplantation. Results: There wasa significant difference in survival rate at 14 days between XHT group (80%), THF group (70%), and N.S group (25%) (P<0.05 V P<0.01).Up to 14 days, In the XHT group , total bilirubin was (7.99 ± 0.58)mg/L and ALT was (55±6.7)u. In the N.S group (9.63±0.83) mg/L V 91 ± 8.0 u, In the FHT group (8.9 0 ±0.66 mg/L) V (74±7.1) u. There wasa significant difference between XHF and control groups. (P<0.05 V P<0.01). CD4,CD8 lymphocytes in the recipient spleens by immunohistochemistry inspected at 12 hr , 72 hr and 14d post -graft respectively. In the XHT group, responsed CD4,CD8 lymphocytes at 72 hr,14d. In the FHT group, There was always masculine. Conclusion: The authors concluded that the survival rate and function of encapsulated xenogenic. hepatocytes were maintained up to 14 days after graft. Cellular immune response participates in the rejection. The immune response can be postponed by XHT.

  • 【分类号】R657.3
  • 【被引频次】1
  • 【下载频次】56
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