青葙皂苷对小鼠心肌梗死的保护作用及机制研究

Protective effect of Celosins on myocardial infarction in mice and its mechanism

目的研究青葙皂苷对小鼠心肌梗死的保护作用,并探讨其作用机制。方法将100只C57/B6小鼠随机分为正常对照组(5%西黄蓍胶溶液)、模型对照组(5%西黄蓍胶溶液)、青葙皂苷小剂量(10mg·kg^-1·d^-1)、中剂量组(30mg·kg^-1·d^-1)和大剂量组(90mg·kg^-1·d^-1)。除正常对照组外其他4组小鼠均结扎冠状动脉左前降支建立心肌梗死模型。各组C57/B6小鼠造模前1周开始给药,造模后继续给药4周,采用Vevo2100系统检查小鼠心功能,酶联免疫吸附法测定血清白细胞介素(IL)-1β、IL-18、心肌肌钙蛋白T(cT-nT)、肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平,心脏切片经2,3,5-氯化三苯基四氮唑(TTC)染色后测定心脏梗死面积,Western blot检测心肌组织核转录因子-κBp65(NF-κBp65)、隐热蛋白(NLRP3)、凋亡相关点样蛋白(ASC)和Caspase-1p45蛋白的表达。结果(1)青葙皂苷可呈剂量依赖性降低心肌梗死小鼠左室收缩末期内径(LVESD)和左室舒张末期内径(LVEDD),升高左室射血分数(LVEF)和左室短轴缩短率(LVFS),差异均有统计学意义(P<0.05);(2)青葙皂苷可呈剂量依赖性降低心肌梗死小鼠血清cT-nT、CK-MB和LDH水平(P<0.05);(3)青葙皂苷可呈剂量依赖性降低心肌梗死小鼠血清IL-1β和IL-18水平(P<0.05);(4)青葙皂苷可呈剂量依赖性抑制心肌梗死小鼠的心肌梗死面积(P<0.05);(5)青葙皂苷可呈剂量依赖性抑制心肌梗死小鼠心肌NF-κBp65、NLRP3、ASC和Caspase-1 p45蛋白表达(P<0.05)。结论青葙皂苷对心肌梗死具有保护作用,其作用可能与其调控NLRP3/ASC/Caspase-1信号通路有关。

Objective To study the protective effect of Celosins on myocardial infarction in mice and explore its mechanism. Methods A total of 100 C57/B6 mice were randomly divided into the normal control group (5% Gummi Tragacanthae solution),the model control group (5% Gummi Tragacanthae solution),the low-dose of Celosins group (10 mg·kg^-1·d^-1 ),the medium-dose group (30 mg·kg^-1·d^-1 ) and the high-dose group (90 mg·kg^-1·d^-1 .Myocardial infarction model was established in 4 groups in addition to the normal control group.Medication in C57/B6 mice of all group 1 week before modeling and continued 4 weeks after modeling.Cardiac function was determined by Vevo 2100 system.Serum interleukin (IL)- 1β,IL-18,cardiac troponin T (cT - nT),creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay.Cardiac infarction area was determined by 5-triphenyltetrazolium chloride (TTC) staining in heart slice.Expression of nuclear transcription factor-κB p65(NF-κB p65),NOD-like receptor P3(NLRP3),apoptosis-related specular proteins (ASC) and Caspase-1 p45 protein in myocardial tissue were determined by Western blot. Results (1) Celosins reduced the left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD),left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in myocardial infarction mice with a dose-dependent manner (P<0.05).(2) Celosins reduced the serum cT-Nt,CK-MB and LDH levels in myocardial infarction mice with a dose-dependent manner (P<0.05).(3) Celosins reduced the serum IL-1 and IL-18 level in myocardial infarction mice with a dose-dependent manner (P<0.05).(4) Celosins reduced the myocardial infarction area in myocardial infarction mice with a dose-dependent manner (P<0.05).(5)Celosins reduced the protein expression of NF-κB p65,NLRP3,ASC and Caspase-1 p45 in myocardial infarction mice with a dose-depentent manner (P<0.05). Conclusion Celosins has protective effect on myocardial infarction,which may be related to the regulation of NLRP3/ASC/Caspase-1 signaling pathway.