氢化可的松对严重脓毒症伴心肌损伤大鼠循环及心肌炎症介质的影响

目的观察不同剂量氢化可的松（HC）对埃希大肠杆菌（E.cdi）致严重脓毒症伴心肌损伤大鼠循环中及心肌炎症介质的影响。方法灭活E．coli二次注射法建立Wistar大鼠严重脓毒症合并心肌损伤模型。40只雄性大鼠随机均分为5组：正常对照组、模型组、大剂量组（HC150mg／kg）、中剂量组（20mg／ks）和小剂量组（6mg／kg）,给药后2h采血及左右心室肌标本,检测血浆心肌肌钙蛋白Ⅰ（cTnⅠ）、肿瘤坏死因子α（TNF—α）、IL-1β、NO、总NOS和心肌匀浆上清液NO、总NOS,并观察心肌iNOS表达情况。结果模型组上述指标均较正常对照组显著升高（P〈0．05）。小剂量组cTnⅠ与正常组无显著性差异,大、中剂量组cTnⅠ反较模型组明显升高。三种剂量HC对血浆TNF—α无明显影响,但均可降低IL-1β,以小剂量更显著,与正常对照组无显著差异;大、中剂量HC均未能降低血浆NO、总NOS,小剂量则能显著降低两者水平（P均〈0．05）;左、右心室肌匀浆含量差异无统计学意义。正常组心肌细胞无iNOS表达,模型组强表达。随HC剂量的递减,iNOS表达逐级减弱。结论不同剂量HC对严重脓毒症大鼠循环中及心肌炎症介质的影响不尽相同,小剂量可明显降低上述炎症介质水平、对心肌细胞iNOS表达的抑制也最显著。提示小剂量HC对严重脓毒症大鼠的心肌损伤有一定的保护作用。

Effects of hydrocortisone on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli

OBJECTIVE: Severe sepsis and septic shock remain the most common cause of death in intensive care units. The main causes of death in sepsis are the cardiac dysfunction and hypotension resistant to cateolamines. The prevalence of relative adrenal insufficiency in severe sepsis and septic shock was estimated at about 32%-51%. Several meta-analysis demonstrated that high-dose glucocorticoids decreased survival during sepsis, while stress doses of corticosteroids may benefit these patients. The exact reason for such widely divergent outcome produced by different doses of corticosteroid is still not understood. Therefore, the study was undertaken to observe the effects of different doses of hydrocortisone (HC) on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli (E. coli). METHODS: The model was established by two injections of inactivated E. coli Forty male Wistar rats were randomly divided into five groups: high-dose of HC group (150 mg/kg), medium-dose group (20 mg/kg), low-dose group (6 mg/kg), model group (NS substituted for HC), and control group (NS for E. coli and HC). Each group had eight rats. After 2 hours of treatment, specimens were collected to measure serum cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO) and total NO synthase (NOS). NO and total NOS in myocardial homogenate were also detected. The expression of inducible NOS (iNOS) of myocytes was investigated. RESULTS: All the above-mentioned markers in model group significantly higher than those in control group. After HC injection, serum cTnI concentrations in low-dose group decreased to normal values compared to that of model group, while in another two HC groups, the concentrations were higher than those in model group. TNF-alpha level was not significantly influenced. But IL-1beta level declined to normal values, being prominent in low-dose HC group. Neither high-dose nor middle-dose HC could lower serum NO or total NOS, but low-dose HC could greatly inhibit both NO and NOS levels (P < 0.05). There was no significant difference in the level of NO and total NOS of myocardial homogenate between left and right ventricles. There was no iNOS expression by normal myocardium, while the expression in model group was significantly increased. After HC injection, the iNOS expressions by myocardium in three HC groups were weaker than those in model group. The intensity of iNOS signals became weak with the decrease in HC dose. CONCLUSION: Different doses of HC might exert different effects on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by E. coli Low-dose HC could significantly inhibit such mediators as well as iNOS expression by cardiomyocytes. The results suggest that low dose HC exert protective effect on myocardial injury of severe septic rats.