Neu-p11对脓毒症大鼠心肌抑制的改善作用  

Protective effects of Neu-pll on myocardial depression in rats with sepsis

作　　者：黄靓[1,2] 王汉群[2] 熊文昊[2] 张弛[1,3] 高勇强[2] 尹卫东[1] 

机构地区：[1]南华大学心血管病研究所,湖南衡阳421001 [2]南华大学外科学总论教研室,湖南衡阳421001 [3]南华大学机能学实验中心,湖南衡阳421001

出　　处：《中国新药与临床杂志》2013年第11期912-915,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：湖南省高等学校科学研究项目(No11C1093)

摘　　要：目的观察Neu-p11对脓毒症大鼠心肌抑制的影响及其机制。方法 45只SPF级雄性SD大鼠随机分为假手术组、脓毒症组和Neu-p11组,每组15只。采用盲肠结扎穿刺法制作脓毒症大鼠模型,Neu-p11组术前7 d每日腹腔注射Neu-p11 15 mg·kg^(-1)。造模成功12 h后经右颈总动脉左心室内插管监测各组大鼠左心室功能指标,同时检测血清心肌肌钙蛋白Ⅰ(cTnI)、脑钠素(BNP)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)的含量,Western blotting法测定心肌组织p38丝裂原活化蛋白激酶(p38MAPK)蛋白表达。结果与假手术组比较,脓毒症组左心室收缩压(LVSP)降低、左心室舒张末期压(LVEDP)升高、左心室等容收缩期压力最大上升/下降速率(±dp/dt_(max))降低,血清cTnI、BNP、TNF-α、IL-6含量和心肌p38MAPK表达均升高(P<0.05或P<0.01)。与脓毒症组相比,Neu-p11组LVSP和±dp/dt_(max)升高、LVEDP降低,血清cTnI、BNP、TNF-α、IL-6含量和心肌p38MAPK表达均降低(P<0.05或P<0.01)。结论 Neu-p11可改善脓毒症状态下心脏功能,其机制可能与降低血清TNF-α、IL-6以及抑制心肌p38MAPK活化有关。AIM To investigate the effects of Neu-pll on cardiac function in rats with sepsis and its mechanism. METHODS Forty- five male Sprague- Dawley rats were randomized into sham operation group, sepsis group and Neu-pll group （15 rats in each group）. Rat models of sepsis were established by cecal ligation and puncture （CLP） and intraperitoneal injection of Neu-pl 1 15 mg·kg-1 daily 7 days before operation in the Neu-pll group. At 24 h after successful modeling, left ventricular function was monitored, and serum concentrations of cardiac troponin- I （cTn I ） , brain natriuretic peptide （BNP） , tumor necrosis factor-α （TNF- α） and interleukin- 6 （IL-6） were measured. And the expression of p38MAPK was detected with Western blotting. RESULTS Cardiac function of sepsis group was depressed markedly by measuring the LVSP, LVEDP, and ±dp/dtmax compared with sham operation group （P 〈 0.05 or P 〈 0.01）. The contents of cTn I , BNP, TNF-α, IL-6 and expression of p38MAPK in sepsis group were significantly higher than those in the sham operation group （P 〈 0.05 or P 〈 0.01 ）. Compared with the sepsis group, LVSP and ±dp/dtmax, were increased and LVEDP, contents of cTn I , BNP, TNF-OL, IL-6 and expression of p38MAPK were decreased in the Neu-pll group （P 〈 0.05 or P 〈 0.01）. CONCLUSION Neu-pll can down-regulate TNF-α and IL-6 levels and inhibit p38MAPK expression, which may be the mechanism for its effect of myocardial protection in septic rat.

关 键 词：Neu-p11 受体 褪黑激素 脓毒症 P38丝裂原活化蛋白激酶类 心脏功能 

分 类 号：R972[医药卫生—药品]