【摘要】 目的探讨磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)通路在红景天苷对急性一氧化碳中毒(ACOP)心肌损伤治疗过程中的作用。方法 48只大鼠经腹腔注射一氧化碳(CO)制作ACOP模型成功后,随机分为4组,分别经尾静脉注射红景天苷10 mg/kg(红景天苷组)、红景天苷10 mg/kg加PI3K/Akt拮抗剂0.5 mg/kg(合并拮抗剂组)、红景天苷10mg/kg加PI3K/Akt激动剂0.5 mg/kg(合并激动剂组)、0.9%氯化钠注射液5 m L/kg(对照组)。24 h后记录生存率,检测血天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)水平。HE染色用于观察心肌病理变化,用ELISA法测定心肌组织中白细胞介素6 (IL-6)、肿瘤坏死因子α(TNF-α)、核因子kB (NF-kB),缺氧诱导因子-1α(HIF-1α)水平,用流式细胞仪检测心肌细胞悬液中PI3K/Akt/HIF-1α表达水平。结果与对照组、合并拮抗剂组比较,红景天苷组、合并激动剂组存活率明显较高,AST、LDH、CK、CK-MB水平较低,差异均有统计学意义(均P<0.05)。拮抗剂组及对照组心肌纤维排列紊乱伴部分肌纤维断裂,而红景天组与激动剂组心肌纤维排列整齐,无肌纤维断裂。与对照组、合并拮抗剂组比较,红景天苷组、合并激动剂组心肌组织IL-6、TNF-a、NF-kB水平均较低,HIF-1α、PI3K/Akt/HIF-1α表达水平较高,差异均有统计学意义(均P<0.05)。结论 PI3K/Akt通路在红景天苷改善CO引起的心肌损伤中起重要作用。更多还原

【Abstract】 Objective To explore the role of phosphatidylinosition-3-kinase/Akt(PI3K/Akt) pathway in the therapeutic effect of salidroside on myocardial damage induced by acute carbon monoxide poisoning(ACOP). Methods Forty-eight rats were randomly divided into Salidroside group, antagonist group, agonist group and control group, and injected with salidroside(10 mg/kg), salidroside(10 mg/kg) plus PI3K/Akt antagonist(0.5 mg/kg), Salidroside(10 mg/kg)plus PI3K/Akt agonist(0.5 mg/kg), and normal saline(5 m L/kg), respectively, through caudal vein after ACOP model was established by intraperitoneal injection of carbon monoxide. 24 hours later, the survival rate was recorded, serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase(CK) and creatine Kinase-MB(CK-MB)were measured. HE staining was used to observe pathological changes of myocardial structure. ELISA was applied to detect myocardial expression of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), nuclear factor-kB(NF-kB) and hypoxia inducible factor-1α(HIF-1α). The flow cytometry was applied to detect the expression of PI3K/Akt in cardiomyocyte suspension. Results The survival rate was significantly higher and AST、LDH、CK、CK-MB were significantly lower in salidroside group and agonist group than in antagonist group and the control group(all P<0.05).Disarray and partial rupture of myocardial fibers were seen in antagonist group and the control group, and not in salidroside group and agonist group. The expression of IL-6, TNF-α and NF-kB was significantly lower and the expression of HIF-1α and PI3K/Akt/HIF-1α in was significantly higher in salidroside group and agonist group than in antagonist group and the control group(all P<0.05). Conclusion The PI3K/Akt pathway plays an important role in the improving effect of salidroside on carbon monoxide-induced myocardial damage.更多还原