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长谷川无白蛋白血症大鼠白蛋白水平的长期纠正:在再生反应下通过移植正常肝细胞使肝脏重新填充。

Long-term correction of albumin levels in the Nagase analbuminemic rat: repopulation of the liver by transplanted normal hepatocytes under a regeneration response.

作者信息

Moscioni A D, Rozga J, Chen S, Naim A, Scott H S, Demetriou A A

机构信息

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

出版信息

Cell Transplant. 1996 Jul-Aug;5(4):499-503. doi: 10.1177/096368979600500409.

Abstract

Numerous studies have reported successful transplantation of hepatocytes with demonstration of function. However, none have shown long-term correction of a liver-related metabolic defect. Male Nagase analbuminemic rats, immunosuppressed with cyclosporin-A, were transplanted with normal hepatocytes (2 x 10(7) cells/rat) isolated from allogeneic male Sprague-Dawley rat donors. Hepatocytes were selectively transplanted via the portal vein tributary into the posterior liver lobes of Nagase analbuminemic rats. Following 2 wk, to allow engraftment, selected transplanted rats (Group I) were reoperated and the portal venous branch supplying the anterior liver lobes was permanently ligated, resulting in their atrophy and induction of regeneration in the residual transplant-bearing lobes. Control rats consisted of: Group II-transplanted with normal hepatocytes without portal branch ligation; Group III-transplanted with analbuminemic hepatocytes with portal branch ligation; and Group IV-nontransplanted analbuminemic rats with portal branch ligation. The experimental period extended to 3 mo posttransplantation. All rats transplanted with normal hepatocytes demonstrated a significant elevation in serum albumin levels (ELISA). Group I rats had dramatic elevations in serum albumin to near normal levels (1.78 +/- 0.20 g/dl), and maintained these levels until the end of the experiment. Albumin levels in Group II rats reached 0.26 +/- 0.07 g/dl (p < 0.001), whereas Group III and IV rats showed no changes in serum albumin levels throughout the experiment. Immunohistology of liver tissue obtained from Group I rats, demonstrated large numbers (22.6 +/- 7.5%) of albumin-positive hepatocytes populating the recipient liver. This is the first report of near-total and sustained correction of a genetic defect in liver function in an experimental animal model following allogeneic hepatocyte transplantation.

摘要

众多研究报告了肝细胞移植成功并证明其具有功能。然而,尚无研究表明能长期纠正肝脏相关代谢缺陷。用环孢素A免疫抑制的雄性长谷川无白蛋白血症大鼠,被移植了从同种异体雄性斯普拉格-道利大鼠供体分离的正常肝细胞(2×10⁷个细胞/大鼠)。肝细胞通过门静脉分支被选择性地移植到长谷川无白蛋白血症大鼠的后肝叶。2周后,为使肝细胞植入,对选定的移植大鼠(第一组)再次手术,将供应前肝叶的门静脉分支永久结扎,导致前肝叶萎缩并诱导剩余移植肝细胞所在肝叶的再生。对照大鼠包括:第二组——移植正常肝细胞但未结扎门静脉分支;第三组——移植无白蛋白血症肝细胞并结扎门静脉分支;第四组——未移植但结扎门静脉分支的无白蛋白血症大鼠。实验期延长至移植后3个月。所有移植正常肝细胞的大鼠血清白蛋白水平(酶联免疫吸附测定)均显著升高。第一组大鼠血清白蛋白急剧升高至接近正常水平(1.78±0.20 g/dl),并维持该水平直至实验结束。第二组大鼠的白蛋白水平达到0.26±·07 g/dl(p<0.001),而第三组和第四组大鼠在整个实验过程中血清白蛋白水平无变化。对第一组大鼠肝脏组织进行免疫组织学检查,显示受体肝脏中有大量(22.6±7.5%)白蛋白阳性肝细胞。这是关于同种异体肝细胞移植后实验动物模型中肝功能遗传缺陷近乎完全且持续纠正的首篇报道。

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