CAJ | 학술논문

目的探讨重组人肝再生增强因子( rhALR)对缺血再灌注(IR)肾损伤大鼠模型肾脏局部炎性细胞浸润及炎性因子表达的影响.方法将SD大鼠按随机数字表法分成假手术组、IR组、rhALR低剂量(100 μg/kg)组及rhALR高剂量(200 μg/kg)组.采用双侧肾蒂夹闭60 min后再灌注建立IR肾损伤动物模型.常规生化法检测血肌酐、尿素氮的水平,HE染色观察肾脏组织学改变,比色法检测肾组织髓过氧化物酶( MPO)的活性,Western印迹法检测肾组织肿瘤坏死因子α(TNF-α)、细胞间黏附分子1(ICAM-1)、单核细胞趋化蛋白1(MCP-1)的蛋白表达.结果 rhALR组的血肌酐和尿素氮显著低于IR组(均P＜ 0.05),肾组织病理损害减轻,rhALR高剂量组较rhALR低剂量组肾功能及肾脏病理改善更明显.IR组大鼠肾组织的MPO活性、TNF-α、ICAM-1、MCP-1的蛋白表达在术后12 h较假手术组显著上升,术后24h有所下降,但仍维持在较高水平(均P＜0.05)；rhALR组肾组织MPO活性、肾组织TNF-α、ICAM-1、MCP-1的蛋白表达较IR组显著下降(均P＜0.05),且rhALR高剂量组4者较rhALR低剂量组下降更显著(均P＜0.05).结论 rhALR对IR肾损伤具有保护作用,其作用机制可能与其减少肾脏局部的炎性细胞浸润、抑制炎性因子MCP-1、ICAM-1、TNF-α的表达有关.
목적 탐토중조인간재생증강인자( rhALR)대결혈재관주(IR)신손상대서모형신장국부염성세포침윤급염성인자표체적영향.방법 장SD대서안수궤수자표법분성가수술조、IR조、rhALR저제량(100 μg/kg)조급rhALR고제량(200 μg/kg)조.채용쌍측신체협폐60 min후재관주건립IR신손상동물모형.상규생화법검측혈기항、뇨소담적수평,HE염색관찰신장조직학개변,비색법검측신조직수과양화물매( MPO)적활성,Western인적법검측신조직종류배사인자α(TNF-α)、세포간점부분자1(ICAM-1)、단핵세포추화단백1(MCP-1)적단백표체.결과 rhALR조적혈기항화뇨소담현저저우IR조(균P＜ 0.05),신조직병리손해감경,rhALR고제량조교rhALR저제량조신공능급신장병리개선경명현.IR조대서신조직적MPO활성、TNF-α、ICAM-1、MCP-1적단백표체재술후12 h교가수술조현저상승,술후24h유소하강,단잉유지재교고수평(균P＜0.05)；rhALR조신조직MPO활성、신조직TNF-α、ICAM-1、MCP-1적단백표체교IR조현저하강(균P＜0.05),차rhALR고제량조4자교rhALR저제량조하강경현저(균P＜0.05).결론 rhALR대IR신손상구유보호작용,기작용궤제가능여기감소신장국부적염성세포침윤、억제염성인자MCP-1、ICAM-1、TNF-α적표체유관.
Objective To investigate the effects of recombinant human augmenter of liver regeneration (rhALR) on renal inflammation in acute kidney injury (AKI) induced by renal ischemia reperfusion (IR). Methods SD rats were randomly divided into sham-operated group,IR group,rhALR1 group (100 μg/kg) and rhALR2 group (200 μg/kg).Both renal pedicles of rats were identified and occluded with microvascular clamps for 60 min to induce acute kidney injury (AKI).Blood urea nitrogen and serum creatinine levels were evaluated using a Hitachi 747 automatic analyzer. For histological examination, sections were stained with HE. The activity of myeloperoxidase (MPO) was detected by spectrophotometer.Expression of TNF-α,ICAM-1,MCP-1 was determined by Western blotting. Results Blood urea nitrogen,serum creatinine levels and the injury of kidney were improved significantly in rhALR group as compared with IR group (all P＜ 0.05).They were improved more significantly in rhALR2 group as compared to in rhALR1 group (all P＜0.05).The protein levels of TNF-α,ICAM-1,MCP-1 and the activity of MPO in kidneys from the sham-operated rats were low,and increased significantly after renal ischemia reperfusion injury (all P＜0.05).After treated with rhALR,the expression of TNF-α,ICAM-1,MCP-1 and the activity of MPO were decreased significantly in kidneys as compared to those in IR group (all P＜0.05),which decreased more significantly in rhALR2 group than those in rhALR1 group (all P＜ 0.05). Conclusions nhALR can protect kidneys from ischemia reperfusion injury in rats.The mechanism may be associated with the inhibition of renal inflammatory cells infiltration and down-regulated expressions of YNF-α,ICAM-1 and MCP-1 in the kidney.