黄芩素脂质聚合物纳米粒对大鼠心肌缺血再灌注损伤的作用机制研究  

Effects of baicalein-loaded lipid-polymer nanoparticles on myocardial ischemia-reperfusion injuries in rats and its mechanism

作　　者：吴萌 李祥平 项艳[1] 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)

机构地区：[1]丽水市中医院药剂科,浙江丽水323000 [2]烟台市纳米药物与高端制剂重点实验室,烟台药物研究所,山东烟台264000

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)。

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.

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 

分 类 号：R285.5[医药卫生—中药学]