人脐带间充质干细胞治疗急性肝功能衰竭大鼠的疗效

目的 探讨人脐带间充质干细胞(hUCMSCs)对急性肝功能衰竭大鼠的治疗效果.方法 腹腔注射D-氨基半乳糖(D-gal)和脂多糖(LPS)诱导大鼠急性肝功能衰竭.将造模成功的大鼠经腹腔或尾静脉移植hUCMSCs,同时将注射0.9%氯化钠溶液的大鼠作为对照组.在第0、1、2、3、5、7天分别检测ALT、TBil和Alb,第7天处死大鼠,观察其肝脏组织病理学改变.统计学方法采用Fisher确切概率法、非配对t检验和Mann-Whitney U检验.结果 腹腔或尾静脉移植hUCMSCs组大鼠存活率与对照组相比,差异均无统计学意义(Fisher确切概率法,均P=1.00).腹腔移植hUCMSCs组大鼠移植后2 d ALT、TBil、Alb分别为(804.9±88.0)U/L、(17.4±2.7)μmol/L、(20.9±0.8)g/L,对照组分别为(1294.3±171.4)U/L、(32.3±5.5)μmol/L、(16.1±0.9)g/L(t=2.640,P=0.020;r=2.529,P=0.025;t=-3.833,P=0.002).尾静脉移植hUCMNCs组肝功能指标改善情况与腹腔移植组相似.腹腔和尾静脉移植hUCMSCs组肝组织损伤程度比对照组轻(U=4.500,P=0.005;U=4.500,P=0.008),肝细胞分裂相指数也有显著提高(U=4.000,P=0.005;U=5.500,P=0.013).结论 经腹腔或尾静脉移植hUCMSCs均可促进急性肝功能衰竭大鼠ALT、TBil、Alb等指标恢复正常,新生肝细胞增殖活跃,同时明显改善肝组织损伤病理分级.

Abstract：

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute liver failure ( ALF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS) in rats. Methods The ALF model was obtained through intraperitoneal injection of D-gal(300 mg/kg)and LPS (20μg/kg)in Wister rats. The hUCMSCs were transplanted after intoxication. All rats were divided into four groups, and each group received either hUCMSCs or 0.9% NaCl solution through intraperitoneal or tail-intravenous injection. To evaluate the liver function of each group, the levels of alanine aminotransferase (ALT), total bilirubin (TBil) and serum albumin (Alb) were measured on the day of hUCMSCs transplantation and the following 1, 2, 3, 5 and 7 days. All rats were then sacrificed to examine the liver histology at day 7. Analyses were done by using Fisher's exact test, unpaired t test and Mann-Whitney U test. Results There were no significant differences of survival rates among four groups (Fisher's exact test, both P = 1. 00). The levels of ALT, TBil and Alb in group receiving hUCMSCs intraperitoneally were (804. 9 ± 88. 0) U/L,(17. 4±2. 7) μmol/L and (20. 9±0. 8) g/L, respectively after 2 days of injection, whereas in the corresponding control group, those were (1294. 3± 171. 4) U/L, (32. 3±5. 5) μmol/L and (16. 1±0. 9) g/L, respectively, which indicated that hUCMSCs transplantation significantly improved the liver function (t = 2. 640, P =0.020;t=2.529, P = 0. 025;t= - 3. 833, P = 0. 002). Both of hUCMSCs-transplanted groups showed no significant differences. Liver histological data showed that transplantation of hUSMSCs through either intraperitoneal or tail-intravenous injection alleviated liver damage (U=4. 500, P = 0. 005;U=4. 500, P = 0. 008) and the mitotic index also increased in hUCMSCs-transplanted groups (U=4. 000, P = 0. 005; U=5. 500, P = 0. 013). Conclusions The levels of ALT, TBil and Alb can rapidly normalize in ALF rats after injected with hUCMSCs either intraperitoneally or tail-intravenously. hUCMSCs application raises the mitotic index, enhances hepatocellular regeneration and improves histological status.

Therapeutic effects of human umbilical cord mesenchymal stem cell transplantation on acute liver failure in rats

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute liver failure ( ALF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS) in rats. Methods The ALF model was obtained through intraperitoneal injection of D-gal(300 mg/kg)and LPS (20μg/kg)in Wister rats. The hUCMSCs were transplanted after intoxication. All rats were divided into four groups, and each group received either hUCMSCs or 0.9% NaCl solution through intraperitoneal or tail-intravenous injection. To evaluate the liver function of each group, the levels of alanine aminotransferase (ALT), total bilirubin (TBil) and serum albumin (Alb) were measured on the day of hUCMSCs transplantation and the following 1, 2, 3, 5 and 7 days. All rats were then sacrificed to examine the liver histology at day 7. Analyses were done by using Fisher's exact test, unpaired t test and Mann-Whitney U test. Results There were no significant differences of survival rates among four groups (Fisher's exact test, both P = 1. 00). The levels of ALT, TBil and Alb in group receiving hUCMSCs intraperitoneally were (804. 9 ± 88. 0) U/L,(17. 4±2. 7) μmol/L and (20. 9±0. 8) g/L, respectively after 2 days of injection, whereas in the corresponding control group, those were (1294. 3± 171. 4) U/L, (32. 3±5. 5) μmol/L and (16. 1±0. 9) g/L, respectively, which indicated that hUCMSCs transplantation significantly improved the liver function (t = 2. 640, P =0.020;t=2.529, P = 0. 025;t= - 3. 833, P = 0. 002). Both of hUCMSCs-transplanted groups showed no significant differences. Liver histological data showed that transplantation of hUSMSCs through either intraperitoneal or tail-intravenous injection alleviated liver damage (U=4. 500, P = 0. 005;U=4. 500, P = 0. 008) and the mitotic index also increased in hUCMSCs-transplanted groups (U=4. 000, P = 0. 005; U=5. 500, P = 0. 013). Conclusions The levels of ALT, TBil and Alb can rapidly normalize in ALF rats after injected with hUCMSCs either intraperitoneally or tail-intravenously. hUCMSCs application raises the mitotic index, enhances hepatocellular regeneration and improves histological status.