摘要
目的 观察TAT肽修饰的载黄芩素(Bai)脂质聚合物纳米粒(Bai-TAT-LPNs)对心肌缺血再灌注损伤大鼠的作用及潜在机制。方法 纳米沉淀法构建Bai-TAT-LPNs;建立心肌缺血再灌注损伤模型大鼠,以Bai作为阳性对照药,在缺血前4 h腹腔注射Bai-TAT-LPNs;生理记录仪和血生化仪检测大鼠血流动力学和血清指标变化;TUNEL染色检测心肌细胞凋亡;蛋白印记实验检测心肌cleaved-caspase 3、Bcl-2、p-Akt蛋白表达变化。结果 Bai-TAT-LPNs外观呈均一的球形,平均粒径为(127.0±2.6)nm。Bai-TAT-LPNs(含Bai 100 mg/kg)可显著升高模型大鼠LVDP、+dp/dt_(max)和-dp/dt_(max)(P<0.01);降低血清LDH、CK、MDA水平,并升高SOD水平(P<0.01);还可抑制心肌细胞凋亡(P<0.01)。同时,Bai-TAT-LPNs下调模型大鼠心肌cleaved-caspase 3蛋白表达,并上调Bcl-2和p-Akt蛋白表达(P<0.01)。Bai-TAT-LPNs的上述作用均优于Bai。结论 Bai-TAT-LPNs可改善大鼠心肌缺血再灌注损伤,且效果优于Bai;该作用可能与增强药物穿膜作用、减轻氧化损伤和激活Akt信号有关。
Objective To observe the effects of TAT peptide-modified baicalein(Bai)-loaded lipid-polymer nanoparticles(Bai-TAT-LPNs)on myocardial ischemia-reperfusion rats and mechanism of action.Methods Bai-TAT-LPNs were prepared by nanoprecipitation method;myocardial ischemia-reperfusion model rats were established and Bai was used as a positive control drug,and Bai-TAT-LPNs were injected intraperitoneally 4 h before ischemia;changes in hemodynamics and serum indexes were detected by physiological recorder and blood biochemistry;myocardial apoptosis was detected by TUNEL staining;protein blotting assay was performed to detect myocardial cleaved-caspase 3,Bcl-2 and p-Akt protein expression.Results Bai-TAT-LPNs had a homogeneous spherical appearance with a mean particle size of(127.0±2.6)nm.Bai-TAT-LPNs(containing Bai 100 mg/kg)significantly increased LVDP,+dp/dt_(max) and-dp/dt_(max)(P<0.01);the levels of LDH,CK and MDA in serum were decreased,and the levels of SOD were increased(P<0.01);the apoptosis of cardiomyocytes was inhibited(P<0.01).Meanwhile,Bai-TAT-LPNs down-regulated myocardial cleaved-caspase 3 protein expression and up-regulated Bcl-2 and p-Akt protein expression in model rats(P<0.01).All of the above effects of Bai-TAT-LPNs were superior to those of Bai.Conclusion Bai-TAT-LPNs ameliorate myocardial ischemia-reperfusion injury in rats with better effect than Bai;this effect may be related to enhanced drug penetration,attenuation of oxidative damage and activation of Akt signaling.
作者
吴萌
李祥平
项艳
Wu Meng;Li Xiangping;Xiang Yan(Department of Pharmacy,Lishui Hospital of Traditional Chinese Medicine,Lishui 323000,China;Yantai Key Laboratory of Nanomedicine and High-end Preparations,Yantai Institute of Pharmaceutical Science,Yantai 264000,China)
出处
《实用药物与临床》
2024年第1期1-5,共5页
Practical Pharmacy and Clinical Remedies
基金
丽水市科技计划项目(2020SJZC068)。
关键词
黄芩素
TAT肽
脂质聚合物纳米粒
心肌缺血再灌注损伤
Baicalein
TAT peptide
Lipid-polymer nanoparticles
Myocardial ischemia-reperfusion injuries
