丹皮酚对心肌纤维化模型大鼠的干预效果及作用机制研究
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山西医科大学省级博士启动基金项目(SD1807);山西医科大学校级博士启动基金项目


Intervention effect and mechanism of paeonol on myocardial fibrosis model rats
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    摘要:

    【摘要】目的 探讨丹皮酚对心肌纤维化模型大鼠的干预效果及作用机制。方法 选取60只雄性SPF级SD大鼠,其中50只用于构建心肌纤维化大鼠模型,40只成功建立心肌纤维化模型,随机分为模型组、低剂量丹皮酚组(10mg·kg-1)、中剂量丹皮酚组(15mg·kg-1)、高剂量丹皮酚组(20mg·kg-1)各10只,另选取正常组10只。检测大鼠左心室舒张末期压力(LVEDP)、左心室收缩压(LVSP)、左心指数;观察心肌组织病理改变;计算心肌胶原容积分数(CVF);酶联免疫吸附试验检测超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、乳酸脱氢酶(LDH)、天门冬氨酸氨基转移酶(AST)、肌氨酸酐致活酶MB(CKMB)水平;Western blot检测TGFβ1/Smad3通路相关蛋白。结果 低、中、高剂量丹皮酚组大鼠左心指数、CVF、MDA、LDH、AST、CKMB低于模型组,LVEDP、LVSP、SOD、CAT水平高于模型组(P<005)。高剂量丹皮酚组大鼠左心指数、CVF、MDA、LDH、AST、CKMB低于低、中剂量丹皮酚组,LVEDP、LVSP、SOD、CAT水平高于低、中剂量丹皮酚组(P<005)。低、中、高剂量丹皮酚组大鼠TGFβ1、Smad2、Smad3蛋白水平低于模型组(P<005)。高剂量丹皮酚组TGFβ1、Smad2、Smad3蛋白水平低于低、中剂量组(P<005)。结论 丹皮酚能够改善大鼠心功能,通过激活TGFβ1/Smad3通路调控氧化应激相关因子水平,从而抑制心肌纤维化发展。

    Abstract:

    【Abstract】Objective To study the intervention effect and mechanism of paeonol on myocardial fibrosis model rats.Methods By establishing myocardial fibrosis model, 10 rats were randomly divided into model group, low dose paeonol group (10mg kg -1), middle dose paeonol group (15mg kg -1), high dose paeonol group (20mg kg -1), and 10 rats in normal group. The left ventricular enddiastolic pressure (LVEDP), left ventricular systolic pressure (LVSP) and left ventricular index were measured. The pathological changes of myocardium were observed. Collagen volume fraction (CVF) and enzymelinked immunosorbent assay (ELISA) were calculated. Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine inactivating enzyme MB (creat MB) were detected by the attached test. Western blot was used to detect TGFβ1/Smad3 pathwayrelated proteins.Results The left ventricular index, CVF, MDA, LDH, AST and CKMB in low, medium and high dose paeonol group were lower than those in model group, while the levels of LVEDP, LVSP, SOD and CAT were higher than those in model group (P<005). The left ventricular index, CVF, MDA, LDH, AST and CKMB in highdose paeonol group were lower than those in lowdose paeonol group and middledose paeonol group, while the levels of LVEDP, LVSP, SOD and CAT were higher than those in lowdose paeonol group and middledose paeonol group (P<005). The expression of TGFβ 1, Smad2 and Smad3 in low, medium and high dose paeonol group were lower than that in model group (P<005). The expression of TGFβ 1, Smad2 and Smad3 in highdose paeonol group were lower than that in lowdose and middledose paeonol group (P<005).Conclusion Paeonol can improve the cardiac function of rats by activating the TGFβ1/Smad3 pathway, regulate the levels of oxidative stressrelated factors, and inhibite the development of myocardial fibrosis.

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  • 在线发布日期: 2020-02-13
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