巨噬细胞移动抑制因子对大鼠糖皮质激素释放及其受体的影响

目的 评价巨噬细胞移动抑制因子(MIF)对大鼠糖皮质激素释放及其受体的影响.方法 实验Ⅰ性SD大鼠32只,体重250-300g,随机分为4组(n=8),对照组(C组)经右侧股静脉注射生理盐水1 ml;重组MIF(rMIF)低剂量组(rMIF-L组)、rMIF中剂量组(rMIF-M组)及rMIF高剂量组(rMIF-H组)分别经右侧股静脉注射rMIF 50、100、200 ng.分别于注射前即刻(T0)、注射后5 min、3、6、12及24 h(T1-3)时,取股动脉血样0.5 ml,测定血清皮质酮浓度.实验Ⅱ DMEM培养液中培养的乳鼠(出生2-3 d)心肌细胞,随机分为3组(n=24),对照组(C组)不做任何处理;rMIF-L组、rMIF-M组分别加入rMIF 50、100 ng,孵育3 h后采用Western blot法测定心肌细胞糖皮质激素受体及热休克蛋白90(HSP9O)的表达.结果 实验Ⅰ与C组比较,rM-L组、rMI-M组及rMIF-H组T1-5时血清皮质酮浓度升高(P<0.05);三组间差异无统计学意义(P>0.05).实验Ⅱ与C组比较,rMIF-L组和rMIF-M组心肌细胞HSP90表达下调(P<0.05);两组问差异无统计学意义(P>0.05);三组间糖皮质激素受体表达差异无统计学意义(P>0.05).结论 脓毒血症时MIF可通过下调HSP90表达,减弱糖皮质激素受体功能,诱发糖皮质激素抵抗.

Effects of macrophage migration inhibitory factor on glucocorticoid release and glucocorticoid receptor in rats

Objective To investigate the effects of macmphage migration inhibitory factor (MIF) on glucocorticoid (GC) re]ease and glucocorticoid recer (GR) in mts.Methods Test Ⅰ Thirty-two male SD rats weighing 250-300 g were randomly divided into 4 groups(n=8 each):control group(C),low dose recombinant MIF (rMIF) group (rMIF-L),middle dose rMIF group (rMIF-M) and high dose rMIF group (rMIF-H).The animals received l ml normal saline via the right femoral vein in group C.The animals received rMIF50.100 and 200 ng in l ml normal saline though right femoral vein in group rMIF-L,rMIF-M or rMIF-H respectively.Blood samples were taken from left femoral artery immediately before inection(T0,baseline),and at 5 min,3 h,6 h.12 h and 24 h after injection of rMIF(T1-5) for determination of serum concentration of corticosterone.Test Ⅱ Primary cultured neonate rat(2-3 days)myocardial ceils were randomly divided into 3 groups(n=24 each):group C,group rMIF-L and group rMIF-M.The ceUs in group C,rMIF-L and rMIF-M wefe incubated with DMEM.rMIF 50 ng+DMEM and rMIF 100 ng+DMEM for 3 h respectively.The expression of GR and HsPg0 wag determined by Western blot.ResuBs Test Ⅰ The serum concentration of corticosterone was signifieemily higher in the other 3 groups than in group C at T1-5(P<0.05).The sertlm concentration of corticostemne was significantly increased at T1-5 in group rMIF-L,rMIF-M and rMIF-H compared with the baseline values(P<0.05).Test Ⅱ HSP90 expresion was significantly lower in the other two groups than in group C(P<0.05).Them was rio signifieanf difference in HSP90 expression between group rMIF-L and group rMIF-M(P>0.05).There was no significant difference in GR expression among the 3 groups ( P > 0.05). Conclusion MIF druing sepsis can weaken GR function through down-regulating HSP9O expression, resulting in CC resistance.