缺血预处理可上调肝再生过程中Hedgehog信号通路的表达  

Expression of Hedgehog signal pathway in liver regenation can upregulate under ischemic preconditioning

作　　者：王文杰[1,2] 杨建旭[2] 余海波[3] 孙荣青[1] 

机构地区：[1]郑州大学第一附属医院,郑州450052 [2]河南省人民医院中心ICU,郑州450003 [3]河南省人民医院肝胆外科

出　　处：《医药论坛杂志》2016年第4期8-11,共4页Journal of Medical Forum

基　　金：河南省科技厅基础与前沿技术项目(112300410037)

摘　　要：目的探讨缺血预处理(IPC)对大鼠肝再生过程中Hedgehog(Hh)信号通路的影响。方法健康成年SD大鼠24只,随机分为3组,分为假手术组(SO组)、缺血再灌注损伤组(IRI组),缺血预处理组(IPC组)。SO组仅作开、关腹处理。IRI组和IPC组先切除肝左内叶、肝左外叶和肝中叶,建立肝再生模型,IRI组在切除部分肝叶前用无损伤的血管夹夹闭第一肝门20 min。IPC组在夹闭第一肝门前,预先阻断第一肝门5min,再灌注10min,余同IRI组。分别留取3组动物术后48 h血清和肝组织。采用蛋白免疫印迹法(Western blot)联合免疫组化方法检测肝组织Shh、Ihh、Gli-1蛋白表达情况,免疫组化法检测肝组织Ki-67表达情况,全自动生化分析仪检测各组血清ALT水平。结果 Shh、Ihh、Gli-1表达水平IPC组表达高于IRI组及SO组(P<0.05),其中IRI组高于SO组(P<0.01或P<0.05)。ki-67阳性细胞数IPC组明显高于IRI、SO组(P<0.05),且IRI组高于SO组(P<0.05)。血清ALT水平IPC组高于IRI组,但无统计学意义(P>0.05),IPC组和IRI组均高于SO组(P<0.05)。结论缺血预处理可通过上调Hh信号通路的表达增强肝脏再生能力,其对缺血再灌注损伤的保护作用,可能与此有关。Objective To investigate the effect of ischemic preconditioning on Hedgehog signal pathway in liver regeneration. Methods Twenty four Healthy male SD rats were randomly assigned into three groups： ① Sham operation group（ SO）; ②Ischemic reperfusion group（ IRI） 70% hepatectomy was performed solely; ③Ischemic preconditioning（ IPC）.SO group： animals were subjected to laparotomy,surgical simulation only. In IRI and IPC groups,liver regeneration model was firstly set up by resection of median and left lobes of liver. IRI group： animals were subjected to ischemia for 20 minutes before partial hepatectomy performed. IPC group： animals were firstly subjected to ischemia for 5 minutes,and then reperfuse for 10 minutes,thirdly performed as IRI group. Blood and hepatic tissues were collected 48 h after the operation in all three groups. The expression of Sonic hedgehog（ Shh）,Indian hedgehog（ Ihh）,Glioblastoma-1（ Gli-1）,in hepatic tissue were detected by Western blot. The expression of Ki-67 was detected by immunohistochemical staining. Plasma ALT was determined by standard auto-analyzer methods. Results Compared with group SO,the expression of Shh,Ihh,Gli-1 in IRI（ P〈0. 01） and IPC（ P〈0. 01） group were significantly elevated,and group IPC higher than that of the group IRI（ P〈0. 01）. The Ki-67 positive cells was significantly more in group IRI and group IPC（ P〈0. 01） compared with group SO. In addition,the Ki-67 positive cells in group IPC were significantly more than those of the group IRI（ P〈0. 01）. The ALT level of group IP was higher than group IR（ P〈0. 05）,but there was no statistical significance. Compared to group SO,the ALT level of IP and IR group was significantly higher（ P〈0. 01）. Conclusion Expression of Hedgehog signal pathway may be up regulated after ischemic preconditioning in rats,which may protect liver from ischemia reperfusing injury.

关 键 词：缺血预处理 肝再生 HEDGEHOG信号通路 

分 类 号：R-332[医药卫生]