摘要
目的:探讨丹参注射液通过调控血管内皮生长因子(VEGF)/VEGF受体2(VEGFR2)和磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路对糖尿病心肌病(DCM)大鼠血管新生的影响及效应机制。方法:建立DCM模型大鼠,将大鼠分为模型组、缬沙坦(40mg/kg,灌胃)组、丹参(2mL/kg,腹腔注射)组,另取正常大鼠作为对照组,每组12只。干预4周后,超声仪和生化法检测大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、二尖瓣E峰/A峰(Em/Am)、空腹血糖(FBG)、空腹胰岛素(FINS)、肌酸激酶同工酶(CK-Mb)、心肌肌钙蛋白I(cTnI)水平;HE和Masson染色观察心肌病理及纤维化情况;免疫荧光染色检测心肌新生血管密度(MVD);Western blot检测心肌中VEGF、VEGF受体2(VEGFR2)、磷酸化PI3K(p-PI3K)、PI3K、磷酸化AKT(p-AKT)、AKT蛋白表达。结果:与对照组比较,模型组大鼠LVEF、LVFS、Em/Am水平降低,FBG、FINS、CK-Mb、cTnI水平升高(P<0.05);心肌结构紊乱,纤维断裂间隙增大,细胞肥大并伴炎症细胞浸润,心肌胶原纤维占比升高(P<0.05);心肌组织中VEGF、VEGFR2、p-PI3K/PI3K、p-AKT/AKT蛋白表达水平降低(P<0.05)。与模型组比较,缬沙坦组和丹参组大鼠LVEF、LVFS、Em/Am水平升高,FBG、FINS、CK-Mb、cTnI水平降低(P<0.05);心肌结构较规整,纤维断裂与间隙缩小,细胞形态正常化,炎症浸润轻微,心肌胶原纤维占比降低(P<0.05);心肌组织中VEGF、VEGFR2、p-PI3K/PI3K、p-AKT/AKT蛋白表达水平升高(P<0.05)。与缬沙坦组比较,丹参组大鼠上述指标水平均无明显差异(P>0.05)。结论:丹参可能通过调控VEGF/VEGFR2和PI3K/AKT信号通路,促进心肌血管新生,从而减轻DCM大鼠心肌损伤。
Objective:To investigate the effect and underlying mechanism of Danshen injection on endothelial angiogenesis in diabetic cardiomyopathy(DCM)rats via modulation of the vascular endothelial growth factor(VEGF)/VEGF receptor 2(VEGFR2)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:A DCM rat model was established and the rats were randomly divided into model group,valsartan(40mg/kg,ig)group,and Danshen(Salvia miltiorrhiza)(2mL/kg,ip)group;with normal rats serving as the control group(n=12 each group).After 4-week intervention,echocardiography and biochemical assays were used to measure left-ventricular ejection fraction(LVEF),left-ventricular fractional shortening(LVFS),mitral E/A ratio(Em/Am),fasting blood glucose(FBG),fasting insulin(FINS),creatine kinase-MB(CK-MB),and cardiac troponin I(cTnI).Myocardial histopathology and fibrosis were evaluated by HE and Masson staining;microvessel density(MVD)was determined by immunofluorescence;and myocardial protein expression of VEGF,VEGFR2,phosphorylated PI3K(p-PI3K),total PI3K,phosphorylated AKT(p-AKT),and total AKT was detected by Western blot.Results:Compared with the control group,the model group exhibited decreased LVEF,LVFS,and Em/Am,and increased FBG,FINS,CK-MB,and cTnI(P<0.05);disordered myocardial architecture,enlarged inter-fiber gaps,hypertrophied cardiomyocytes with inflammatory infiltration,and elevated collagen fraction(P<0.05);and reduced myocardial expression levels of VEGF,VEGFR2,p-PI3K/PI3K,and p-AKT/AKT(P<0.05).Relative to the model group,both valsartan and Danshen(Salvia miltiorrhiza)group exhibited increased levels of LVEF,LVFS,and Em/Am,and decreased levels of FBG,FINS,CK-MB,and cTnI(P<0.05);ameliorated myocardial structure,attenuated fiber rupture and collagen deposition,and lessened inflammatory infiltration(P<0.05);and up-regulated expression levels of VEGF,VEGFR2,p-PI3K/PI3K,and p-AKT/AKT(P<0.05).No significant differences in the above indices were observed between the valsartan and Danshen(Salvia miltiorrhiza)group(P>0.05).Conclusion:Danshen may attenuate myocardial injury in DCM rats by promoting endothelial angiogenesis via activation of the VEGF/VEGFR2 and PI3K/AKT signaling pathway.
作者
郭艳敏
郑宪玲
刘昱良
张树杰
谭珊
张志佳
GUO Yanmin;ZHENG Xianling;LIU Yuliang(Handan Central Hospital,Hebei Handan 056001,China)
出处
《河北医学》
2026年第2期183-189,共7页
Hebei Medicine
基金
河北省卫生健康委医学科学研究课题,(编号:20231940)
邯郸市科学技术研究与发展计划项目,(编号:23422083017ZC)。
