PI3K/Akt通路在红景天苷治疗急性一氧化碳中毒心肌损伤中的作用

The role of PI3K/Akt pathway in therapeutical effect of Salidroside on myocardial damage induced by acute carbon monoxide poisoning

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10 mg/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 mL/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。

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 mL/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-αand NF-kB was significantly lower and the expression of HIF-1αand PI3K/Akt/HIF-1αin 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.