黄芪甲苷脂质聚合物纳米粒对缺血再灌注损伤诱导大鼠模型的影响

Effects of astragaloside Ⅳ-lipid polymerhybrid nanoparticles on rat model induced by ischemia-reperfusion injury

目的探讨黄芪甲苷脂质聚合物纳米粒(AA-LPNs)对缺血再灌注损伤诱导大鼠模型的影响。方法采用纳米沉淀法制备AA-LPNs。选取16只清洁级SD大鼠,按随机数字表法将其分为常规组(8只)和研究组(8只),常规组给予黄芪甲苷(AA)(40 mg/kg,1.5 ml),研究组给予AA-LPNs(40 mg/kg,1.5 ml),比较两组药代动力学参数[药物半衰期(t_(1/2))、药峰时间(T_(max))、药峰浓度(C_(max))、浓度-时间曲线下面积(AUC)(AUC_(last)、AUC_(all))、平均滞留时间(MRT)(MRT_(last)、MRT_(all))]。另选取60只大鼠,从中随机选取15只作为假手术组,其余构建缺血再灌注损伤诱导大鼠模型,造模成功后按随机数字表法将其分为模型组、AA组、AA-LPNs组,每组15只。造模24 h后,AA组和AA-LPNs组以40 mg/kg剂量灌胃给药,假手术组和模型组给予等量0.9%氯化钠溶液,给药1次/d,连续给药4周。实验结束后,检测四组血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平;采用TUNEL检测四组心肌细胞凋亡情况。结果本研究制备的AA-LPNs呈类球形,均一圆整,平均动态直径为(180±23)nm。研究组的t_(1/2)、T_(max)、AUC_(last)、AUC_(all)、MRT_(all)均高于常规组,差异有统计学意义(P<0.05)。模型组血清CK、LDH、MDA含量及细胞凋亡率均高于假手术组,SOD含量低于假手术组,差异有高度统计学意义(P<0.01)。AA组和AA-LPNs组血清CK、LDH、MDA含量及细胞凋亡率均低于模型组,SOD含量高于模型组,差异有统计学意义(P<0.05或P<0.01)。AA-LPNs组血清CK、LDH、MDA含量及细胞凋亡率均低于AA组,SOD含量高于AA组,差异有统计学意义(P<0.05或P<0.01)。结论AA-LPNs对缺血再灌注损伤大鼠的心肌细胞具有保护作用。

Objective To investigate the effects of astragaloside Ⅳ-lipid polymerhybrid nanoparticles(AA-LPNs)on rat model induced by ischemia-reperfusion injury.Methods AA-LPNs was prepared by nano-precipitation method.Sixteen clean SD rats were selected and divided into the conventional group(8 rats)and the study group(8 rats)according to the random number table method.The conventional group was given astragaloside Ⅳ(AA)(40 mg/kg,1.5 ml),and the study group was given AA-LPNs(40 mg/kg,1.5 ml).The pharmacokinetic parameters of the two groups were compared(drug half-life[t_(1/2)],peak time[T_(max)],peak concentration[C_(max)],area under concentration-time curve[AUC][AUC_(last),AUC_(all)],mean retention time[MRT][MRT_(last),MRT_(all)]).Another 60 rats were selected,15 of which were randomly selected as the sham operation group,and the rest were constructed as ischemia-reperfusion injury induced rat models.After successful modeling,the rats were divided into model group,AA group,and AA-LPNs group according to random number table method,with 15 rats in each group.Twenty four hours after modeling,the AA group and AA-LPNs group were given 40 mg/kg intragastric administration,while the sham operation group and model group were given 0.9% sodium chloride solution,once a day,for consecutive four weeks.After the experiment,the serum levels of creatine kinase(CK),lactate dehydrogenase(LDH),superoxide dismutase(SOD),malondialdehyde(MDA)in four groups were detected.TUNEL assay was used to detect the apoptosis of myocardial cells in the four groups.Results The AA-LPNs prepared in this study were spherical and uniformly round,with an average dynamic diameter of(180±23)nm.t_(1/2),T_(max),AUC_(last),AUC_(all),and MRT_(all) in the study group were higher than those in the conventional group,and the differences were statistically significant(P<0.05).Serum CK,LDH,MDA level and apoptosis rate in model group were higher than those in sham operation group,while SOD level was lower than that in sham operation group,the differences were highly statistically significant(P<0.01).Serum CK,LDH,MDA level and apoptosis rate in AA group and AA-LPNs group were lower than those in model group,while SOD level was higher than that in model group,the differences were statistically significant(P<0.05 or P<0.01).Serum CK,LDH,MDA level and apoptosis rate in AA-LPNs group were lower than those in AA group,while SOD level was higher than that in AA group,the differences were statistically significant(P<0.05 or P<0.01).Conclusion AA-LPNs has a protective effect on myocardial cells in rats with ischemia-reperfusion injury.