丹参对小肠缺血再灌注后肾脏p38MAPK信号通路的影响

Effects of salvia miltiorrhiza on the kidney p38MAPK signal channel induced by intestinal ischemia/reperfusion in rats

目的:观察丹参(Salvia miltiorrhiza)对大鼠小肠缺血再灌注损伤(Ischemia reperfusion injury,IRI)中肾脏p38丝裂素活化蛋白激酶(p38 mitogen-activated protein kinases,p38MAPK)信号转导通路的影响。方法:雄性SD大鼠36只,随机分为空白组、缺血再灌注组、丹参处理组。采用钳闭大鼠肠系膜上动脉缺血再灌注模型。酶联免疫吸附实验(Enzyme-linked immuno-sorbent assay,ELISA)测定肾组织中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和白介素-1β(Interleukin-1β,IL-1β)的含量,蛋白印记(Western blot)法检测肾组织中磷酸化p38丝裂素活化蛋白激酶(Phospho-p38 mitogen-activated protein kinase,P-p38MAPKs)的表达;紫外分光光度法检测血浆二胺氧化酶(Diamine oxidase,DAO)的活性;HE染色形态学方法评价肠及肾组织损伤;血清生化分析仪检测尿素氮(Blood urea nitrogen,BUN)和肌酐(Crea,Cr)。结果:缺血再灌注组与空白组比较,小肠及肾组织结构损伤严重,肾脏中p38MAPK、TNF-α和IL-1β表达明显增高,血浆DAO、BUN、Cr含量升高(P<0.01);丹参处理组与缺血再灌注组比较,肾组织中p38MAPK表达显著降低,肾组织中TNF-α和IL-1β含量减少,血浆DAO含量下降,小肠和肾组织结构损伤显著减轻。BUN、Cr明显降低(P<0.05)。结论:丹参可减轻小肠缺血再灌注肾损伤;其机制与其抑制肾组织中p38MAPK信号转导通路的活化进而减少TNF-α、IL-1β的释放有关。

Objective：To observe the effects of salvia miltiorrhiza Bunge on the kidney p38MAPK signal channel induced by intestinal ischemia/reperfusion in rats.Methods：Thirty-six male Wistar rats were randomly divided into 3 equal groups：control group,ischemia reperfusion injury group and salvia miltiorrhiza group.Intestinal ischemia reperfusion model was constructed by incarcerating rat SMA.Enzyme-linked immunosorbent assay（ELISA） was used to determine protein content of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in kidney tissue.Western blot was used to determine the expression of Phospho-p38 mitogen-activated protein kinase（P-p38MAPKs）.Ultraviolet spectrophotometry was used to determine the activity of plasma DAO.HE staining morphology method was used to evaluate injury severity for intestine and kidney.The biochemical analyser was used to test BUN and Cr.Results：Compared with control group,in IR group,intestine and kidney tissue structures were injured seriously;the expressions of p38MAPKs,TNF-α and IL-1β increased significantly,and the content of DAO,BUN and Cr also increased（P0.01）.Compared with IR group,in S group,the expressions of p38MAPKs,TNF-α and IL-1β were reduced significantly;intestine and kidney tissue structures were injured slightly.The content of DAO,BUN and Cr was also reduced（P0.05）.Conclusion：Salvia miltiorrhiza can relieve kidney injury by intestinal ischemia/reperfusion.The mechanism is possibly connected with the inhibition effect on the kidney p38MAPK signal channel to reduce the release of TNF-α and IL-1β.