骨髓间充质干细胞输注治疗大鼠小体积肝移植术后肝衰竭

目的 探讨大鼠骨髓间充质干细胞输注治疗大鼠小体积肝移植术后肝衰竭的可行性.方法 体外分离、培养、鉴定大鼠骨髓间充质干细胞,采用细胞膜染料PKH26对骨髓间充质干细胞进行标记.将雄性SD大鼠随机分为对照组和治疗组.对照组于小体积(30 %)肝移植术中,在移植肝血供恢复时自尾静脉注入磷酸盐缓冲液(PBS) 0.5 ml,治...     

肝切除术后肝衰竭的防治策略

<正>肝部分切除术是肝脏外科中最常见的术式,是治疗肝脏肿瘤、肝内胆管结石、肝脓肿等疾病的重要手段^[1-2]。然而,大多数患者存在慢性肝脏疾病,尤其是肿瘤患者往往合并有肝炎或肝硬化背景,对肝脏功能造成了不同程度的损害,增加了患者接受肝切除术后发生肝衰竭(post?hepatectomy liver failure,PHLF)的风险。PHLF的发生率为1.2%～32.0%,术后发生PHLF不仅明显延长了患者住院时间,增加了经济负担,同时也是威胁围手术期安全的主要因素^[3-4]。本文对PHLF的相关危险因素、预防措施及治疗手段进行了总结和系统综述,供临床参考。     

肝干细胞移植治疗终末期肝病的进展

近年来,肝干细胞的研究成为全球研究人员所关注的热点,并为各种终末期肝病的治疗开辟了崭新的思路。本文就肝干细胞的来源及其在治疗终末期肝病中的临床应用,以及相关前沿、存在问题和展望作一综述。     

间充质干细胞在肝再生研究中的应用

间充质干细胞(mesenchymal stem cells,MSCs)移植治疗肝损伤及肝衰竭已取得令人瞩目的成就.但是,细胞定植能力弱以及潜在致瘤性、促纤维化的可能,阻碍了MSCs的临床应用.因此,有必要探索更优化的治疗方式,以提高MSCs治疗的安全性及有效性.迄今,MSCs来源的肝细胞、基因修饰的MSCs及MSCs培养液成分运用促进肝再生已取得鼓舞人心的成果.本文就近些年MSCs在肝再生研究中的应用作一综述.     

细胞移植治疗急性心肌梗塞的进展

本文简要综述了骨髓造血干细胞和骨髓间充质干细胞在治疗急性心肌梗死中的应用前景与存在的问题.     

肝胆恶性肿瘤肝切除术后肝衰竭危险因素的meta分析

目的 探讨影响肝胆恶性肿瘤肝切除术后肝衰竭(PHLF)发生的危险因素,为预防及减少PHLF提供参考依据.方法 检索PubMed、中国知网等国内外数据库2011年1月至2020年3月期间收录的关于肝胆恶性肿瘤PHLF危险因素的病例对照研究,采用纽卡斯尔-渥太华量表进行文献质量评价,应用RevMan 5.3软件进行meta...     

MSCs治疗慢性创面的临床研究进展

目的 综述MSCs在慢性创面治疗中的临床研究进展.方法 广泛查阅近年来MSCs治疗慢性创面的相关文献,对MSCs治疗慢性创面的可能机制及其在临床慢性创面治疗中的应用情况、面临问题进行总结.结果 MSCs可参与到慢性创面愈合各个环节来促进创面愈合,在临床试验中展现出广阔应用前景.目前临床研究常用的MSCs包括骨髓来源MS...     

大鼠同种骨髓间充质细胞门静脉输注对肝大部分切除肝衰模型术后肝功能、生存率的影响

目的 观察大鼠同种骨髓间充质细胞(BMSCs)经门静脉肝内移植对80％肝切除肝衰竭模型术后肝功能、生存率的影响.方法 通过80％肝切除建立大鼠边缘肝衰竭模型,经门静脉输注绿荧光蛋白(GFP)标记的第5代(P5)大鼠同种MSC,观察BMSCs肝内移植对肝大部分切除边缘肝衰竭模型术后生存率、肝功能的影响.结果 术后7d内的存活率:MSC组72.2％( 13/18)、对照组44.4％ (8/18).MSC组的存活率明显高于对照组(72.2％比44.4％,P＜0.05;MSC组大鼠术后肝功能恢复情况明显优于对照组(P＜0.05);MSC组肝组织中可观察到移植的细胞.结论 经门静脉的BMSCs移植可促进80％肝切除边缘肝衰竭大鼠的肝功能恢复和提高生存率.     

急性肝衰竭大鼠载肝细胞生长因子纳米粒子肝细胞移植后有丝分裂指数和Ki-67表达变化及意义

目的 探讨急性肝衰竭(ALF)大鼠载肝细胞生长因子(HGF)的聚乳酸-氧-羧甲基壳聚糖(PLA-O-CMC)纳米粒子肝细胞移植后有丝分裂指数和Ki-67抗原的表达变化及意义.方法 D-氨基半乳糖腹腔内注射制作大鼠ALF模型,48 h后分别将Ⅰ型胶原(Ⅰ组)、PLA-O-CMC纳米粒子(Ⅱ、Ⅳ组)、载HGF的PLA-O-CMC纳米粒子(Ⅲ组)培养的大鼠肝细胞(均为5×107个,5 ml)移植到ALF大鼠腹腔内.以每日静脉注射HGF 10μg/kg×7 d(Ⅳ组)、5 Ml RPMI 1640腹腔内注射(Ⅴ组)作为对照.观察其14 d存活率、血清及肝组织HGF浓度、肝组织病理及有丝分裂指数(MI)、Ki-67变化.结果移植后14 d Ⅰ～Ⅴ组ALF大鼠的存活率分别为50.00％、68.75％、81.25％、75.00％、18.75％.各纳米移植组高于V组.Ⅲ组3 d时肝组织HGF浓度最高,平均为5882.91 μG／L.Ⅲ组肝组织结构恢复更快,5 d时平均MI 10.20％0、7 d时平均MI 10.20‰、7 d时Ki-67平均标记指数16.8‰,均高于Ⅴ组.结论 应用载HGF的PLA-O-CMC纳米粒子培养的大鼠肝细胞腹腔内移植治疗ALF大鼠能促进肝再生相关抗原表达.

Abstract：

Objective To evaluate the change and significance of Ki-67 antigen expression follow ing hepatocyte transplantation using hepatocyte growth factor (HGF) loaded polylactic acid-O-carboxymethylchitosan (PLA-O-CMC) nanoparticles in rats with acute liver failure (ALF). Methods ALF models of rats were established by D-galactosamine intraperitoneal injection. Rat hepatocytes type Ⅰ collagen suspension (group Ⅰ ),rat hepatocytes co-cultured with PLA-O-CMC nanoparticles ( groups Ⅱ ,Ⅳ ) and rat hepatocytes co-cultured with HGF loaded PLA-O-CMC nanoparticles ( group Ⅱ ) (5 × 107 cells each group,5 ml) were transplanted into the abdominal cavity of SD rats at 48 h after D-Gal injection. Intravenous injection of HGF ( 10 μg/kg for 7 days) ( group Ⅳ ) and RPMI 1640 injection (group Ⅴ ) were used as the negative groups. The 14th-day survival rate of rats,pathological change and mitotic index of liver,Ki-67 antigen labeling index of ALF rat livers were observed. Results The 14th-day survival rate in groups Ⅰ -Ⅴ was 50.00％,68. 75％,81.25％,75.00％,18.75％,and that in nano-transplanted groups was higher than in group Ⅴ. At the 3rd day,the concentration of HGF in liver tissue of group Ⅲ,average 5882. 91 μg/L was the highest. The hepatic lobules structure in group Ⅲ recovered faster. The average mitotic index in group Ⅱ at the 5th day was 10. 20‰ and the average Ki-67 labeling index at the 7th day was 16. 8‰,which were all higher than in group Ⅴ. Conclusion Intraperitoneal transplantation of HGF loaded PLA-O-CMC nanoparticle-attached hepatocytes for treatment of ALF can promote the liver regenerationassociated antigen expression.     

骨髓间充质干细胞移植重建大鼠缺血心肌的实验研究

目的　探讨大鼠骨髓间充质干细胞 (MSCs)移植于缺血心肌后的增殖分化情况和对缺血心肌细胞的修复重建能力及心功能改善情况。　方法　实验组为将体外培养SD大鼠的MSCs经溴氮胞苷 (BrdU)标记后显微注射于结扎冠状动脉后的大鼠缺血心肌内 ,并以无血清培养基注射动物为对照组。 4周后观察移植细胞的分化情况 ,并通过超声多普勒、心肌核素显像、免疫组化和新生血管形成情况来检测心功能变化。　结果　实验组MSCs移植 4周后 ,在缺血心肌区内可发现不同分化阶段的心肌样细胞。超声检查发现实验组的左室射血分数 (LVEF)的改善明显好于对照组 (P <0 0 5 ) ;SPECT显示实验组心肌核素摄取显著高于对照组 (P <0 0 1) ;在促新生血管形成方面 ,实验组也明显好于对照组(P <0 0 5 )。　结论　骨髓间充质干细胞移植于缺血心肌后可重建缺血心肌 ,增加心肌灌注 ,显著改善心功能。     

Mechanism of liver failure after hepatectomy

Liver failure after hepatectomy is caused by many factors such as excessive hepatectomy, ischemic-reperfusion injury, postoperative infection, etc. However, apoptosis of hepatocytes is the most important event in the molecular mechanism of liver failure. Liver failure after excessive hepatectomy is characterized by increased apoptosis of hepatocytes and diminished liver regeneration. The former is induced by hypercytokinemia and hyperendotoxemia, and the latter is caused by cell cycle arrest. In ischemic-reperfusion injury of the liver, the apoptosis of hepatocytes is caused by activation of the MMPT and calpain system that are induced by the intracellular accumulation of Ca. The possible mechanism of liver failure in cases with persistent infection is the inhibition of liver regeneration and the induction of apoptosis of hepatocytes due to transforming growth factor-beta 1. The knowledge of these mechanisms will lead to prompt and appropriate treatments for individual patients.     

肝切除术后肝功能衰竭的危险因素

随着肝脏外科技术的发展,围手术期管理和患者筛选标准的进步使可以接受半肝切除术或扩大肝切除术的患者数量大大增加.而肝切除术后肝功能衰竭是肝切除术后严重的并发症之一,肝切除术后肝功能衰竭患者相关风险中糖尿病及已有肝脏疾病如肝硬化、脂肪肝、胆汁淤积等是最重要的危险因素.手术相关风险中残肝体积及术中大出血是影响肝切除术后肝功能衰竭发病率及病死率的关键因素.而到目前为止还没有很好的方法治疗肝功能衰竭,所以预防显得尤为重要.     

Risk factors of liver failure after right-sided hepatectomy

Background

To prevent hepatic failure after major hepatectomy, it is important to assess preoperative factors related to liver failure.

Methods

We examined 80 patients who underwent right-sided hepatectomy. Hyperbilirubinemia, uncontrolled ascites, and prolonged postoperative hospital stay were defined as liver failure after hepatectomy, and these 3 factors were evaluated in relation to clinicopathological and surgical factors.

Results

In the 80 patients, hyperbilirubinemia was observed in 10 (12.7%) patients, uncontrolled ascites in 18 (22.5%) patients, and prolonged hospital stay after surgery in 39 (48.8%) patients. Multivariate analyses identified platelet count as a risk factor of hyperbilirubinemia, uncontrolled ascites, and prolonged postoperative hospital stay, and the ratio of remnant liver volume to body surface area (RLV/BSA ratio) as an additional risk factor of hyperbilirubinemia and prolonged postoperative hospital stay.

Conclusions

Platelet count and RLV/BSA ratio are useful risk factors for prediction of liver failure after right-sided hepatectomy.     

腹腔镜活体肝移植供肝切取术的临床应用进展

活体肝移植的开展不仅扩大了供者数量,有效缓解器官捐献不足,也降低了患者等待肝移植期间的病死率。近年来,随着腹腔镜技术和器械的不断发展,腹腔镜供肝切取术在活体肝移植领域的应用日益广泛,也是该领域的研究热点之一,其具有创伤小、疼痛少、供者术后恢复迅速且心理负担小等优点。但由于其对供者筛选严格、操作复杂、学习曲线长,目前仍然只在少数移植中心得以开展。本文从腹腔镜活体肝移植供肝切取术的发展历史与现状、具体术式及存在的问题与挑战进行介绍,展望腹腔镜供肝切取术的未来发展方向,为促进其在活体肝移植中的进一步发展,改善活体肝移植预后提供参考。     

Relevance of two-stage total hepatectomy and liver transplantation in acute liver failure and severe liver trauma

Emergency liver transplantation frequently is the only life-saving procedure in cases of acute liver failure. It remains unclear whether emergency hepatectomy with portocaval shunt followed by liver transplantation as a two-stage procedure should be performed in cases in which a donor organ is not yet available. It has been stated that “toxic liver syndrome” could be treated by means of this strategy. From 1990 to 1995 we performed emergency hepatectomies in eight cases of acute liver failure or traumatic liver rupture with exsanguinating bleeding. In six cases we were able to perform a subsequent liver transplantation. Five of the six patients who underwent an emergency hepatectomy died. Emergency hepatectomy led to a significant increase in epinephrine dosage until the transplantation was performed. Only after transplantation did the need for epinephrine therapy decrease. The need for oxygen support did not change during the entire observation period. Plasmatic coagulation was stabilized by substitution, showing significantly higher values at 24 h after transplantation than at 48 h before transplantation. Fibrinogen increased significantly after transplantation in this group of patients. The experiences gathered at our clinic, however, do not show advantages that would allow a recommendation of emergency hepatectomy and subsequent liver transplantation as a two-stage procedure except for situations of severe and uncontrollable hepatic bleeding. Considering the progressive destabilization of our patients, fast procurement of donor organs seems to be of imminent importance for the outcome. Received: 4 October 1999 Revised: 18 July 2000 Accepted: 23 November 2000     

肝移植治疗肝硬化肝癌切除术后肝功能衰竭:附二例

肝移植是治疗肝癌切除术后肝功能衰竭的有效手段。我院分别于2001年及2004年对2例肝硬化肝癌切除术后肝功能衰竭病人进行了肝移植治疗，现总结报道如下。[第一段]     

Native hepatectomy after auxiliary partial orthotopic liver transplantation

In countries where a living donor is the only source of the graft, the limited size of the graft is of serious concern when considering extending the procedure to adult recipients. In order to overcome this problem, auxiliary partial orthotopic liver transplantation (APOLT) was applied to the concept that the residual native liver would support the graft function until the graft expanded enough to work by itself. We herein report on a 20-year-old woman with primary sclerosing cholangitis (PSC), who received a small-size liver graft by APOLT. Computed tomography and scintigraphy showed that the graft had regenerated sufficiently 1 month after the operation. The diseased residual native liver is potentially carcinogenetic. Therefore, second-stage native hepatectomy was done 35 days after the first operation. Histopathologic examination of the resected native liver revealed biliary cirrhosis with PSC but no evidence of cholangiocarcinoma. Second-stage native hepatectomy after APOLT seems to be a curative treatment for chronic end-stage liver disease with graft size mismatch that may be as good as orthotopic liver transplantation. Received: 22 October 1998 Received after revision: 15 January 1999 Accepted: 26 February 1999     

Rescue hepatectomy for initial graft non-function after liver transplantation

BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.