聚乳酸-O-羧甲基壳聚糖纳米粒子培养的猪肝细胞移植对大鼠急性肝衰竭的治疗作用  

The Therapeutic Effect of Porcine Fepatocyte Transplantation Using Polylactic Acid-O-carboxymethylated Chitosan Nanoparticles on Rats with Acute Liver Failure

作　　者：张春辉[1] 陈钟[1] 杨欣荣[1] 戴新征[1] 祝文彩[1] 

机构地区：[1]南通大学附属医院普外科,江苏南通226001

出　　处：《中国临床医学》2008年第1期58-62,共5页Chinese Journal of Clinical Medicine

基　　金：江苏省卫生厅重大项目基金(H200215);南通大学创新基金(CX0301)

摘　　要：目的：探讨胶原凝胶包埋的聚乳酸-O-羧甲基壳聚糖纳米粒子培养的猪肝细胞腹腔内移植对急性肝衰竭（ALF）大鼠的治疗效果。方法：D-氨基半乳糖腹腔内注射制作大鼠ALF模型。48h后分别将培养24h的猪肝细胞悬液（含5.0×10^7个肝细胞，I组）、I型胶原凝胶固定培养24h的猪肝细胞（含5.0×10^7个肝细胞，Ⅱ组）、I型胶原凝胶包埋的PL-A-O-CMC纳米粒子培养24h的猪肝细胞（含5.0×10^7个肝细胞，Ⅲ组）移植到ALF大鼠腹腔内，并以RPMIl640腹腔内注射作为对照（IV组）。观察移植后大鼠14d存活率，血清白蛋白（ALB）、谷丙转氨酶（ALT）、总胆红素（TB）、血氨（NH3）的变化和移植肝细胞的病理变化。结果：移植后14d ALF大鼠的存活率：I组为56.25％，Ⅱ组为62.5％，Ⅲ组为75％，Ⅳ组为18.75％，各移植组高于对照组（P＜O.05）。移植后1～5d，I、Ⅱ、Ⅲ组各项肝功能指标改善明显优于Ⅳ组，Ⅲ组肝功能恢复好于同时间其它移植组，肝功能恢复从快到慢依次为Ⅲ、Ⅱ、I、Ⅳ组。Ⅲ组移植肝细胞存活时间最长，炎症浸润最轻。结论：应用胶原凝胶包埋的聚乳酸-O-羧甲基壳聚糖纳米粒子培养的猪肝细胞腹腔内移植治疗ALF大鼠能显著改善肝功能、提高生存率，聚乳酸-O-羧甲基壳聚糖纳米粒子用于异种肝细胞移植具有良好的生物相容性，并能延长移植肝细胞的存活时间。关键词肝细胞移植；急性肝衰竭；聚乳酸-O-羧甲基壳聚糖；Objective： To evaluate the therapeutic effect of intraperitoneal transplantation of porcine hepatocytes cultured with polylactic acid-O-carboxymethylated chitosan （PLA-O-CMC） nanoparticles and embedded in collagen gel on acute liver failure （ALF） rats induced by D-galactosamine （D-Gal）. Methods：At 48h after D-gal introperitoneal injection, free porcine hepatocytes suspension （5.0x 10^7 hepatocytes, group I ）, porcine hepatocytes embedded in collagen gel （5.0x 10^7 hepatocytes, group II ） and porcine hepatocytes cultured with PLA O-CMC nanoparticles and embedded in collagen gel （5.0x 10^7 hepatocytes, group Ⅲ） were transplanted into peritoneal cavity of SD rats, respectively, RPMI 1640 medium was injected into peritoneal cavity of SD rats as control group （group Ⅳ）, The 14d survival rate, liver functions such as ALB, ALT, TB, NH3 level and the pathological change of transplanted hepatocytes were observed, Results： The 14d survival rate in groups Ⅰ, Ⅱ, Ⅲ and Ⅳ was 56. 25%, 62.5%, 75%0 and 18.75%, respectively. It was higher in groups Ⅰ,Ⅱ, Ⅲ than group IV （P〈0.05）. The results showed that liver functions were quickly restored in groups Ⅰ, Ⅱ and Ⅲ compared with those in group Ⅳ during 5 days posttransplantation. The improvement of the liver functions in group Ⅲ was the most quick. The second was group Ⅱ and the third was group Ⅰ The slowest one was group Ⅳ in all groups. The survival time of transplanted porcine hepatocytes was longest and the level of infiltration of inflammatory cells was lightest in group Ⅲ. Conclusion： Intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can increase the survival rate of ALF rats induced by D-Gal and improve liver functions of the damaged recipient significantly, PLA-O-CMC nanoparticles have the better bio-compatibility in hepatocytes xenotransplantation and can prolong the survival time of the transplanted hepatovcytes.

关 键 词：肝细胞移植 急性肝衰竭 聚乳酸-O-羧甲基壳聚糖 纳米粒子 

分 类 号：R575.3[医药卫生—消化系统]