环孢霉素A联合脾内肝细胞移植治疗急性肝衰竭的实验研究

Therapeutic Effects of CsA Combined with Hepatocyte Intrasplenic Transplantation on Acute Hepatic Failure

目的探讨应用环孢霉素A(CsA)与同种异体肝细胞脾内移植联合治疗大鼠急性肝衰竭的疗效.方法采用硫代乙酰胺(TAA)诱导大鼠急性肝衰竭模型,24 h后随机分为三组:Ⅰ组:脾内注射浓度约为2×107个/mL肝细胞悬液1 mL,肌肉注射CsA 10 mg/(kg.d);Ⅱ组:仅脾内注射约2×107个/mL肝细胞悬液1 mL,不用CsA;Ⅲ组:仅脾内注射生理盐水1 mL,作为空白对照.观察各组存活率、肝功能、肝脏病理变化及脾内移植肝细胞的存活情况.结果Ⅰ组、Ⅱ组1周存活率显著高于Ⅲ组(64.7%vs 12.5%,P<0.01;56.3%vs 12.5%,P<0.01),但Ⅰ组和Ⅱ组之间比较无显著性差异(64.7%vs 56.3%,P>0.05).肝功能及病理情况在Ⅰ组、Ⅱ组有明显改善,尤以Ⅰ组最为显著.结论 CsA联合同种异体肝细胞移植能有效治疗大鼠急性肝衰竭,改善TAA诱导的肝衰竭大鼠的存活率,促进肝功能恢复及改善肝脏病理状况.

Objective To evaluate the therapeutic effects of CsA combined with allogenic hepatocyte through intrasplenic transplantation on rats with acute hepatic failure.Methods Acute hepatic failure（AHF） rats were induced by 350 mg/kg thioacetamide（TAA）and randomly divided into 3 groups 24 h after intoxication.Rats in Group I received 1ml of approximately 2×107 hepatocytes suspension and CsA 10 mg/（kg.d）,through intrasplenic injection and intramuscular injection.Rats in Group Ⅱ only received 1 mL of approximately 2×107 hepatocytes suspension.Rats in Group Ⅲ as control received 1 ml of normal saline.The survival rate,hepatic biochemical function and pathological changes of transplanted hepatocytes and liver of all rats were observed.Results One-week survival rate in group Ⅰ and group Ⅱ was higher than that of group Ⅲ（64.7% vs 12.5%,P 0.01;and 56.3% vs 12.5%,P 0.01,respectively）,while there was no significant difference in one-week survival rate between group Ⅰ and group Ⅱ（64.7% vs 56.3%,P0.05）.Hepatic function and liver pathological state of rats were improved significantly in group Ⅰ and group Ⅱ,especiall in group I.Conclusion CsA combined with allogenic hepatocyte transplantation can effectively treat rats with acute hepatic failure,improve the survival rate of rats,and ameliorate hepatic function and hepatic pathological state.