肾上腺髓质素对大鼠肾脏损伤早期肿瘤坏死因子及其受体表达的影响

Experimentation and investigation of the effects of TNF and the acceptor expression in renal early trauma with extragenous adrenomedullin

目的探讨外源性肾上腺髓质素（ADM）对肾脏机械性损伤早期肿瘤坏死因子（TNF-α、TNF—β）及TNF受体（TNFR）表达的影响。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）和伤后给药组（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机械性损伤模型。两给药组分别于创伤前、后10min腹腔注射ADM（0．1 nmol／kg）。3组肾损伤大鼠平均分为4批分别于创伤后1、6、12和24h，采用快速心脏采血法处死。迅速解剖动物提取肾脏标本，10％甲醛固定。免疫组织化学染色，观察肿瘤坏死因子TNF-α、TNF-β、TNFR在组织中的表达，并进行统计学分析。结果TNF—α表达：单纯创伤组在创伤早期（1、6h）高于正常对照组；伤前给药组创伤后6h，伤后给药组创伤后1h均低于同时相点单纯创伤组，差异均具有统计学意义（P〈0．05，P〈0．01）。TNF—β表达：单纯创伤组于伤后1、6h均低于正常对照组，差异均具有统计学意义（P〈0．05）；伤后给药组伤后1、6h均高于单纯创伤组同时相点，差异均具有统计学意义（P〈0．01）。TNFR表达：单纯创伤组于创伤后6h低于正常对照组（P〈0．01）；伤前给药组伤后1、6h高于同时相点单纯创伤组，差异均具有统计学意义（P〈0．01）。结论TNFR对TNF-α与TNF-β具有动态调节作用且以TNF-α为主。TNF-β在肾脏损伤中主要参与的是抗损伤过程。ADM能降低TNF—α的分泌，在肾损伤早期可以上调TNF—β和TNFR。

Objective To investigate the effects of TNF-α, TNF-β and the acceptor expression about mechanical renal trauma with extraneous ADM. Methods There were 104 healthy adult plain grade Wister rat, randomly divided into four groups：8 in the group of control, 32 in the group of trauma, 32 in the group injected ADM before trauma, 32 in the group injected ADM post trauma. The experimental model of rat kidney with mechanical trauma was prepared by striking the area of rat skin reflecting by kidney with free dropping ferrous hammer in the last three groups. ADM （0. 1 nmol/kg）administrated by intrapertoneal injection at 10 minutes before trauma or post trauma respectively in injected groups. All rats were executed by drawing-out all the blood in their hearts. Renal tissue was investigated to study positive expression of TNF-α, TNF-β, TNFR after SABC stained. Results TNF-α expression ： the TNF-α expression of trauma group was more positive than it of control group in the wound early time. The expression of group injected post trauma was less than it of trauma group at 1 h （ P 〈 0. 01 ）. The expression of group injected before trauma was less than it of trauma group at 6 h（ P 〈 0. 05 ） TNF-β expression ： the TNF-β expression of trauma group was less than it of control group at 1 h and 6 h（ P 〈 0. 05 ）. The TNF-β expression of group injected post trauma was more positive than it of trauma group at the same time of 1 h and 6 h （ P 〈 0.01 ）. TNFR expression： the TNFR expression of trauma group was less than it of control group at 6 h（P 〈0. 01 ）. The TNFR expression of group injected before trauma was more positive than it of trauma group in the at the same time of 1 h and 6 h （ P 〈 0. 01 ） . Conclusions The TNFR can regulate the TNF-α and the TNF-β in dynamic balancing. The regulation of TNFR is main to TNF-α. What the TNF-β participated in renal trauma mainly is the anti-damage process. ADM can reduce the expression of TNF-α. ADM increases the expression of TNF-β and TNFR.