AIM: To explore the effects of exogenous adrenomedullin( ADM ) on hypothalamus - pituitary - adrenal cortex ( HPA )axis in the early stage of acute mechanical renal trauma.METHODS: Healthy adult Wistar rats were randomly divided into 4 groups: 8 in control group, 32 in trauma group, 32 in the group injected with ADM before trauma and 32 in the group injected with ADM after trauma.To induce renal trauma, the rats in the latter 3 groups were subjected to mechanical impact directly on the skin of renal region by a free - fall iron hammer.The rats in 2 treatment groups were injected with ADM ( 0.1 nmol/kg ) intraperitoneally 10 min just before and after trauma, respectively.The rats in the 3 groups with kidney injury were executed in batches by drawing all the blood quickly in the hearts at the time points of 1 h, 6 h, 12 h and 24 h after trauma.The hypothalamus tissues were also collected.The expression of corticotropin - releasing hormone( CRH ) in hypothalamus and the concentrations of adrenocorticotropic hormone( ACTH ) and cortisol( CORT ) in plasma were detected by immunohistochemical method and radioimmunoassay.RESULTS: The expression of CRH in hypothalamus and the concentrations of ACTH and CORT in plasma in trauma group, but were slightly higher than those in control group,but without statistical significance.The expression of CRH in hypothalamus at 1 h and 24 h, the concentration of ACTH in plasma at 12 h and CORT at 6 h, 12 h and 24 h in the group injected with ADM before trauma significantly higher than those in trauma group and control group ( P ＜0.05 ).The expression of CRH in hypothalamus at 1 h, 6 h and 12 h and the concentration of CORT in plasma at 12 h and 24 h in the group injected with ADM after trauma were obviously higher than those in trauma group and control group ( P ＜0.05 ).CONCLUSION: Exogenous ADM stimulates HPA axis and activates the function of HPA axis markedly.However, the different layers of HPA axis have different responses to exogenous ADM.Injection of ADM before or after trauma has different effects on HPA axis.%目的:研究外源性肾上腺髓质素(ADM)的运用对肾脏急性机械性损伤早期下丘脑-垂体-肾上腺皮质(HPA)轴的影响,探讨外源性ADM在急性创伤中的生物学作用.方法:健康成年普通级Wistar大鼠104只,随机分为4组:正常对照组(8只)、单纯创伤组(32只)、伤前给药组(32只)、伤后给药组(32只);后3组采用自由落体打击仪直接打击大鼠脊肋区制作肾脏机械性损伤模型.2个给药组分别于损伤前后10 min腹腔注射ADM(0.1 nmol/kg).3 组肾损伤大鼠分为4 批分别于创伤后1、6、12、24 h采用快速心脏采血法处死.迅速解剖动物提取下丘脑标本,采用免疫组化染色法检测促肾上腺皮质激素释放激素(CRH)在下丘脑的表达;放免分析法检测血浆促肾上腺皮质激素(ACTH)、皮质醇(CORT)浓度.结果:单纯创伤组下丘脑CRH的表达及血浆ACTH、CORT浓度较正常对照组轻微升高,但无显著差异;创伤前注射ADM使创伤后下丘脑CRH的表达在1、24 h,血浆ACTH浓度在12 h,以及血浆CORT浓度在6、12、24 h显著高于单纯创伤组及正常对照组(P<0.05);创伤后注射ADM使下丘脑CRH的表达在1、6、12 h,以及血浆CORT浓度在12、24 h明显高于单纯创伤组及正常对照组(P<0.05).结论:外源性ADM可激活HPA轴,使HPA轴各个层面的活动增强,但不同层面对外源性ADM的反应性不同,创伤前、后注射ADM对HPA轴的影响不同.
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