通心络预给药对缺血再灌注损伤心肌的保护作用及肥大细胞脱颗粒诱导炎症反应的机制

Effect of Tongxinluo Preadministration on Myocardial Protection and Inflammatory Response Induced by Mast Cell Degranulation in Ischemia Reperfusion Injury Rats

目的探究通心络预给药对缺血再灌注损伤心肌的保护作用及肥大细胞脱颗粒诱导炎症反应的作用机制。方法将51只心电图正常的大鼠随机分为假手术组、模型组及实验组,每组各17只。给予实验组大鼠通心络超微粉氯化钠溶液灌胃,假手术组及模型组给予等量0.9%氯化钠注射液灌胃,7 d后将模型组及实验组大鼠制备心肌缺血再灌注模型。收集各组大鼠再灌注后心电图,检测血常规、血生化指标,测定血清调节激酶(ERK)、5-羟色胺(5-HT)、脾酪氨酸激酶(Syk)、类胰蛋白酶(TPS)及心肌组织中类糜蛋白酶、β-氨基己糖甘酶水平;测定心肌细胞凋亡指数。结果实验组大鼠心电图ST段上抬程度明显小于模型组(P<0.05);实验组大鼠PLT水平明显低于假手术组及模型组(P<0.05);模型组大鼠WBC计数明显高于假手术组及实验组(P<0.05);模型组大鼠CK与LDH水平明显高于假手术组及实验组(P<0.05);模型组大鼠Ca2+水平明显高于假手术组及实验组,且假手术组大鼠Ca2+水平明显高于实验组(P<0.05);实验组大鼠血清ERK水平明显高于假手术组及模型组,且假手术组大鼠血清ERK水平明显高于模型组(P<0.05);实验组大鼠血清5-HT、Syk及TPS水平明显低于假手术组及模型组,且假手术组大鼠血清5-HT、Syk及TPS水平明显低于模型组(P<0.05);实验组大鼠心肌病理变化较模型组轻微;实验组大鼠心肌组织中类糜蛋白酶、β-氨基己糖甘酶及凋亡指数明显低于假手术组及模型组,且假手术组大鼠心肌组织中类糜蛋白酶、β-氨基己糖甘酶及凋亡指数明显低于模型组(P<0.05)。结论通心络预给药可减少心肌损伤,减轻肥大细胞脱颗粒诱导的炎症,其机制为降低5-HT、Syk等炎性因子水平,上调ERK表达。

Objective To investigate effect of Tongxinluo preadministration on myocardial protection and inflammatory response induced by mast cell degranulation in ischemia reperfusion injury rats.Methods Fifty-one rats with normal electrocardiogram were randomly divided into the sham operation group,model group and experimental group,each with 17 rats.Rats were made into the ischemia reperfusion injury models and received the corresponding treatments.Then various indexes were recorded,including electrocardiogram(ECG),blood routine,biochemical indexes,extracellular signal-regulated kinase(ERK),5-hydroxytryptamine(5-HT),spleen tyrosine kinase(Syk),Tryptase(TPS),chymase andβ-hexosahexosaminase in myocardial tissue as well as the apoptotic index of myocardial cells.Results The elevation of ST segment in the experimental group was significantly lower than that in the model group(P<0.05).The level of PLT in the experimental group was significantly lower than that in the sham operation and the model group(P<0.05).The WBC count in the model group was significantly higher than that in the sham operation and the experimental group(P<0.05),and the levels of CK and LDH in the model group were significantly higher than those in the sham operation and the experimental group(P<0.05).The Ca2+level ranking in a descending order among three groups was the model group,followed by the sham operation group and the experimental group(P<0.05).The ERK level ranking in a descending order among three groups was the experimental group,followed by the sham operation group,and the model group(P<0.05).The levels of 5-HT,Syk and TPS ranking in an ascending order among three groups was the experimental group,followed by the sham operation group and model group(P<0.05).The pathological changes of myocardium in the experimental group were slighter than those in the model group.The chymase,β-hexosahexosaminase in myocardial tissue as well as the apoptotic index of myocardial cells ranking in an ascending order among three groups was the experimental group,followed by the sham operation group,and model group(P<0.05).Conclusion Pre-administration of Tongxinluo can reduce myocardial damage and reduce the inflammation induced by degranulation of mast cells.The mechanism is to reduce the levels of inflammatory factors such as 5-HT and Syk and up-regulate the expression of ERK.