天香丹对冠状动脉微循环障碍大鼠微血管内皮结构及功能的影响

Effects of Tianxiangdan on Microvascular Endothelial Structure and Function in Rats with Coronary Microcirculation Disorders

目的探讨天香丹对冠状动脉微循环障碍(CMD)大鼠微血管结构变化及内皮功能的影响。方法选取雄性Sprague-Dawley(SD)大鼠48只,随机分为假手术组、模型组、天香丹低剂量组、天香丹中剂量组、天香丹高剂量组及尼可地尔组,每组8只。建立大鼠CMD模型,造模完成后,按照体表面积法,假手术组给予生理盐水灌胃,每日2 mL;模型组给予生理盐水灌胃,每日2 mL;天香丹低剂量组给予天香丹灌胃,每日0.81 g/kg;天香丹中剂量组予天香丹灌胃,每日1.62 g/kg;天香丹高剂量组给予天香丹灌胃,每日3.24 g/kg;尼可地尔组给予尼可地尔灌胃,每日1.35 mg/kg,连续给药28 d。观察大鼠心肌微血管超微结构;测定大鼠心肌微血管密度;检测血清一氧化氮(NO)、内皮素-1(ET-1)水平及心肌组织内皮型一氧化氮合酶(eNOS)蛋白表达水平。采用脂多糖(LPS)诱导心肌微血管内皮细胞(CMECs)建立CMECs损伤模型,分为对照组、脂多糖组、天香丹组、脂多糖+天香丹组,检测各组细胞eNOS蛋白的表达水平及上清液NO水平。结果在动物水平上,与模型组比较,天香丹可减轻冠状动脉微血管内皮肿胀、减少微血栓、增加微血管密度(P<0.05),天香丹中剂量组、天香丹高剂量组血清NO水平及NO/ET-1的比值明显升高(P<0.05),心肌组织eNOS蛋白表达水平升高(P<0.05或P<0.01)。在细胞水平上,与脂多糖组比较,脂多糖+天香丹组CMECs内eNOS蛋白表达水平及上清液NO水平增加(P<0.01)。结论天香丹对CMD大鼠心肌微血管结构及内皮功能具有改善作用。

Objective To investigate the effect of Tianxiangdan on microvascular structure and endothelial function in rats with coronary microcirculation disorder(CMD).Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham operation group,model group,Tianxiangdan low-dose group,Tianxiangdan medium-dose group,Tianxiangdan high-dose group,and nicorandil group,with 8 rats in each group.The CMD model of rat was established.After the model was established,the sham operation group was given normal saline by gavage according to the body surface area method,2 mL daily.The model group was given normal saline by gavage,2 mL a day.Tianxiangdan low-dose group was given Tianxiangdan by gavage,0.81 g/kg daily;Tianxiangdan medium dose group was given Tianxiangdan by gavage,1.62 g/kg daily;Tianxiangdan high-dose group was given Tianxiangdan by gavage,3.24 g/kg daily;Nicorandil group was given nicorandil by gavage(1.35 mg/kg daily)for 28 days.The ultrastructure of myocardial microvessel was observed.Myocardial microvessel density was measured.The levels of nitric oxide(NO)and endothelin-1(ET-1)in serum and the expression of endothelial nitric oxide synthase(eNOS)protein in myocardial tissue were detected.Cardiac microvascular endothelial cells(CMECs)were induced by lipopolysaccharide(LPS)to establish CMECs injury model.The cells were divided into control group,lipopolysaccharide group,Tianxiangdan group,and lipopolysaccharide+Tianxiangdan group.Results At the animal level,compared with the model group,Tianxiangdan could reduce coronary microvascular endothelial swelling,reduce microthrombus and increase microvascular density(P<0.05),and the serum NO level and the ratio of NO/ET-1 were significantly increased in Tianxiangdan medium dose group and Tianxiangdan high dose group(P<0.05).The expression level of eNOS protein in myocardial tissue was increased(P<0.05 or P<0.01).At the cellular level,the expression level of eNOS protein in CMECs and the level of NO in supernatant of LPS-Tianxiangdan group were increased compared with those of LPS group(P<0.01).Conclusion Tianxiangdan can improve myocardial microvascular structure and endothelial function in CMD rats.