地塞米松对异丙肾上腺素所致小鼠急性心肌损伤及脾脏 T细胞亚群的影响

摘要

目的：观察地塞米松（DEX ）对异丙肾上腺素（ISO ）致小鼠急性心肌缺血损伤的影响，并探讨其作用机制。方法：16只昆明种小鼠随机分成正常对照组（CON组）、ISO组、DEX预处理组（DEX＋ISO组）、DEX后处理组（ISO＋DEX组），每组各4例。ISO组腹腔注射 ISO （5mg／kg ），1次／天，连续3天；DEX＋ ISO 组于 ISO 注射前30min腹腔注射DEX（1．25mg／kg），连续3天；ISO＋DEX组于实验第2天和第3天腹腔注射ISO后30min ，再腹腔注射DEX（1．25mg／kg）；CON组腹腔注射等量生理盐水，连续3天。实验第4天，各组小鼠心脏采血检测血清谷草转氨酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同功酶（CK‐MB）；摘取心脏进行 HE染色，观察各组心肌组织形态学改变；摘取脾脏，流式细胞术检测脾组织匀浆 T细胞亚群分布。结果：（1）与CON组比较，ISO组AST、LDH、CK均显著升高（P＜0．01）；心肌组织损害明显加重（P＜0．01）；脾组织CD8＋、CD4＋CD69＋ T细胞表达上升（P＜0．05，P＜0．01）。（2）与ISO组比较，DEX＋ ISO组AST、CK、LDH、CK‐MB均下降（P＜0．05或 P＜0．01）；心肌组织损害明显改善（ P＜0．01）；脾组织CD4＋、CD8＋ T细胞表达显著下降（ P＜0．01），CD4＋CD69＋ T细胞表达显著上升（P＜0．01）。（3）与ISO组比较，ISO＋DEX组CD8＋ T细胞表达下降（P＜0．05），其余均无明显变化（P＞0．05）。结论：DEX预处理可以明显改善ISO致小鼠急性心肌缺血损伤，其作用机制可能与DEX介导的 T细胞亚群免疫应答功能改变有关。%Objective:To investigate potential protective effect of glucocorticoid receptor (GR)agonist dexam‐ethasone(DEX) on isoproterenol(ISO)‐induced myocardial injury and the possible mechanism .Method:The sixteen mice were randomly divided into control (CON) group(n= 4) ,ISO group(n= 4) ,dexamethasone pretreatment (DEX+ISO) group (n=4)and dexamethasone treatment(ISO+DEX) group(n=4) .ISO group ,DEX+ ISO group and ISO+DEX group received 5mg/kg isoproterenol hydrochloride ,daily intraperitoneal injection of 1 time ,contin‐uous 3 days .DEX+ISO group given dexamethasone(1 .25mg/kg)injection by intraperitoneal injection as a pretreat‐ment before treatment 30 minutes .At the 2nd and 3rd day ,dexamethasone(1 .25mg/kg) was given after ISO injec‐ted 30 minutes in ISO+DEX group .The serum AST ,LDH ,CK ,and CK‐MB were detected .Myocardial tissue in‐jury was assessed by HE staining .Flowcytometry was adopted to detect the expression of T cell subpopulation .Re‐sults:①Compared with control group ,the levels of AST ,LDH and CK were significantly increased ;the degree of myocardial injury were greatly deteriorated in ISO group (P< 0 .01);the expression 0f CD8+ T cells and CD4+CD69+ T cells were greatly increased(P<0 .05 ,P<0 .01) .②Compared with ISO group ,the levels of AST and CK was significantly reduced(P<0 .01);the levels of LDH and CK‐MB were reduced(P<0 .05);the degree of myocar‐dial injury was greatly improved(P<0 .01) in DEX+ ISO group;the expression of CD4+ T cells and CD8+ T cells were significantly reduced(P<0 .01) ,the expression of CD4+ CD69+ T cells were significantly increased(P<0 .01) in DEX+ISO group .③Compared with ISO group ,the expression of CD8+ T cells were reduced(P<0 .05) and the other wasn't difference (P>0 .05) in ISO+DEX group .Conclusion:DEX pretreatment has protective effect against ISO‐induced myocardial injury .The mechanism might be the transformation of immune function .