Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups ...Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups according to the randomized block design method,and were administered by intragastric administration for 10 consecutive days,and on the 9th and 10th days,rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA.In addition,the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test.The influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ(CaMK Ⅱ)/extracellular regulated protein kinases(ERK)signaling pathway has also been tested.Results: KXA significantly reduced the ISO-induced increase in ST-segment,interventricular septal thickness,cardiac mass index and cardiac tissue pathological changes in rats.Moreover,the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine(NE)or potassium chloride(KCl)was increased after KXA treatment in an endothelium-independent manner,and was attenuated by preincubation with verapamil,but not with tetraethylammonium chloride,4-aminopyridine,glibenclamide,or barium chloride.KXA pretreatment attenuated vasoconstriction induced by CaCl_(2)in Ca^(2+)-free solutions containing K^(+) or NE.In addition,KXA pretreatment inhibited accumulation of Ca^(2+)in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK Ⅱ and p-ERK levels.Conclusion: KXA may inhibit influx and release of calcium and activate the CaMK Ⅱ/ERK signaling pathway to produce vasodilatory effects,thereby improving myocardial injury.展开更多
基金Supported by Natural Science Foundation of Fujian Province(No.2018J01884)Science and Technology Major Project of Fujian Province(No.2019YZ014004)+1 种基金Fujian Provincial Health and Family Planning Commission(No.2018-CX-42)the National Natural Science Foundation of China(No.81774135)。
文摘Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups according to the randomized block design method,and were administered by intragastric administration for 10 consecutive days,and on the 9th and 10th days,rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA.In addition,the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test.The influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ(CaMK Ⅱ)/extracellular regulated protein kinases(ERK)signaling pathway has also been tested.Results: KXA significantly reduced the ISO-induced increase in ST-segment,interventricular septal thickness,cardiac mass index and cardiac tissue pathological changes in rats.Moreover,the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine(NE)or potassium chloride(KCl)was increased after KXA treatment in an endothelium-independent manner,and was attenuated by preincubation with verapamil,but not with tetraethylammonium chloride,4-aminopyridine,glibenclamide,or barium chloride.KXA pretreatment attenuated vasoconstriction induced by CaCl_(2)in Ca^(2+)-free solutions containing K^(+) or NE.In addition,KXA pretreatment inhibited accumulation of Ca^(2+)in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK Ⅱ and p-ERK levels.Conclusion: KXA may inhibit influx and release of calcium and activate the CaMK Ⅱ/ERK signaling pathway to produce vasodilatory effects,thereby improving myocardial injury.
