氯磷酸二钠对急性坏死性胰腺炎大鼠肝损伤的影响

Protective effects of lipsomal clodronate on hepatic injury in rats with acute necrotizing pancrratitis

目的 探讨氯膦酸二钠对急性坏死性胰腺炎（ANP）大鼠肝损伤的保护作用.方法 SD大鼠48只,按随机表法分为对照组、ANP组和氯磷酸二钠组.采用胰腺被膜下均匀注射5%牛磺胆酸钠制作ANP模型.利用薄膜法制备包裹氯磷酸二纳的脂质体.ANP组和氯磷酸二纳组于制模后立即经尾静脉分别注射空白脂质体和包裹氯磷酸二钠的脂质体.制模后2.6 h分批处死动物,取血检测血清淀粉酶（AMS）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）及IL-6、IL-12的含量,取肝脏和胰腺组织,观察病理学变化.结果 对照组、ANP组和氯磷酸二纳组6 h点的ALT含量分别为（73±11）U/L、（257±33）U/L和（184±29）U/L;AST分别为（190±32）U/L、（590±70）U/L和（430±52）U/L;AMS为（814±80）U/L、（5031±471）U/L和（2843±236）U/L;IL-6为（26.7±5.7）pmol/L、（218.0±4.7）pmol/L和（112.3±8.0）pmol/L;IL-12为（4.2±1.0）pmol/L、（309.5±8.5）pmol/L和（153.7±6.3）pmol/L.ANP组和氯磷酸二纳组上述血清指标均显著高于对照组,而氯磷酸二纳组的含量又较ANP组显著降低（P值均〈0.01）.氯磷酸二纳组大鼠的胰腺及肝脏病理变化均较ANP组明显减轻.结论 静脉给予脂质体包裹的氯磷酸二纳对ANP大鼠的肝损伤具有一定保护作用.

Objective To investigate the protective effect of lipsomal clodronate against hepatic injury in rats with acute necrotizing pancreatitis （ANP）. Methods 48 SD rats were randomly divided into control group, ANP group and lipsomal clodronate group, respectively. The models of ANP were established by injection of sodium taurocholate into the pancreatic capsule. Lipsomal clodronate was prepared by means of thin film. Blank liposomes and clodronate-containing liposomes was injected via caudal vein in ANP group and lipsomal clodronate group, respectively. The rats were sacrificed at 2, 6 h after ANP induction, the serum levels of ALT, AST and AMS, IL-6,IL-12 were measured, and pathologic changes of liver and pancreas were observed. Results At 6 h, serum level of ALT was （73 ± 11） U/L, （257 ± 33） U/L and （184 ± 29） U/L in control group, ANP group and lipsomal clodronate group, respectively;serum levels of AST were （190 ± 32）U/L, （590 ± 70）U/L and （430±52）U/L, respectively;serum levels of AMS were （814±80）U/L, （5031 ± 471） U/L and （2843 ± 236） U/L, respectively, serum levels of IL-6 were （26.7 ± 5.7） pmol/L, （218.0 ±4.7）pmol/L and （112.3 ± 8. O） pmol/L, respectively;serum levels of IL-12 were （4. 2 ± 1.0） pmol/L,（309.5 ± 8.5） pmol/L and （153.7 ± 6.3） pmol/L. The values in ANP group and lipsomal clodronate group were significantly higher than those in control group, while the values in lipsomal clodronate group were significantly lower than those in ANP group （P 〈 0. 01）. Pathologic changes of liver and pancreas were significantly attenuated in lipsomal clodronate group. Conclusions Intravenous liposomal clodronate could exert protective effects on the hepatic injury in rats with ANP.