摘要
目的探讨参附注射液对心力衰竭大鼠JAK-STAT信号通路的调节作用。方法将40只SD大鼠随机分为对照组、模型组、参附注射液组、贝那普利组,每组各10只。采用阿霉素腹腔注射法对模型组、参附注射液组、贝那普利组建立慢性心力衰竭大鼠模型。造模成功后,分别给予等容生理盐水、参附注射液0.8 ml/100 g,贝那普利0.045 mg/100 g灌胃,连续干预8周。测定并比较各组大鼠心功能和心肌肥厚指标,心肌组织中白介素6(IL-6)、肿瘤坏死因子(TNF-α)、内皮素、血管紧张素Ⅱ(Ang-Ⅱ)的含量,并采用免疫组化的方法观察大鼠心肌组织JAK1、STAT3蛋白的表达。结果各组大鼠间心功能指标、心肌肥厚指标、IL-6、TNF-α、内皮素、Ang-Ⅱ水平比较,差异均有统计学意义(P均<0.05)。进一步两两比较,参附注射液组、贝那普利组大鼠较模型组各指标均有显著改善(P均<0.05),且参附注射液组在改善左心室收缩压、左心室内压最大上升速率、TNF-α及内皮素水平较贝那普利组更为明显(P均<0.05)。参附注射液组及贝那普利组大鼠JAK1、STAT3蛋白的表达显著高于对照组,低于模型组(P均<0.05),但是两组间比较差异均无统计学意义(P均>0.05)。结论参附注射液通过阻断JAK-STAT细胞信号传导通路的介导,抑制机体细胞因子释放,减少JAK1、STAT3蛋白表达,抑制心肌重塑,改善心肌舒缩功能。
Objective To explore the regulation mechanism of Shenfu injection on Janus kinase （JAK）-signal transducer and activator of transcription （STAT） signaling pathway in rats with chronic heart failure （CHF）, and to explore its possible mechanism. Methods The SD rats were randomized into the normal, model, Shenfu and benazepril groups, 10 rats in each group. The CHF rat model was induced by intraperitoneal injection of small-dose adriamycin in the treatment groups including the model, Shenfu and benazepril groups. After the day of modeling, the treatment groups were given an equal volume of normal saline, Shenfu injection 0.8 ml/100 g and benazepril 0.045 mg/ 100 g respectively by gastrogavage for 8 weeks. Heart function, myocardial hypertrophy index, interleukin-6 （IL-6）, tumor necrosis factor-alpha （TNF-α）, endothelin, angiotensin Ⅱ （Ang-Ⅱ） were evaluated and compared. The expression of JAK1 andSTAT3 were detected by immunohistochemistry. Results The heart function indices, myocardial hypertrophy index, IL-6, TNF-α, endothelin and Ang-Ⅱ in the four groups all showed significant differences （all P 〈 0.05）. All the indices in the Shenfu and benazepril groups were better than those in the model group （all P 〈 0.05）, and levels of the left ventricular systolic pressure, maximum left ventricular developed pressure rate, TNF-α and endothelin in the Shenfu group were much better （all P〈0.05）. Furthermore, the expressions of JAK1 and STAT3 in the Shenfu and benazepril groups were higher than those in the control group, and lower than those in the model group （all P 〉 0.05）. Conclusion Shenfu injection can notably decrease the cytokine release, and the expressions of JAK1 and STAT3 ameliorate myocardial remodeling and improve myocardial systolic and diastolic function by blocking JAK-STAT signaling pathways.
出处
《中华危重症医学杂志（电子版）》
CAS
2014年第1期20-24,共5页
Chinese Journal of Critical Care Medicine:Electronic Edition
基金
浙江省自然科学基金(Q12H270019)
