地尔硫■对大鼠心脏缺血再灌注损伤的保护作用

Protective effect of diltiazem pretreatment on myocardial ischemia reperfusion injury in rat

目的观察地尔硫■对大鼠心脏缺血再灌注损伤(MIRI)的保护作用及机制。方法按照体重将SD大鼠随机分为5组:假手术组、模型组和低、中、高3个剂量实验组,每组12只。模型制备前30 min,低、中、高3个剂量实验组分别腹腔注射50,100,200 mg·kg^(-1)地尔硫■,假手术组及模型组均腹腔注射0. 9%Na Cl 100 mg·kg^(-1)。结扎大鼠冠状动脉左前降支30 min再灌注40 min建立MIRI模型。以酶联免疫吸附法检测大鼠心肌白细胞介素-10(IL-10)、白细胞介素-1β(IL-1β)和肿瘤坏死因子(TNF-α)水平;用Image J图像分析系统测定心肌梗死面积百分比。结果假手术组、模型组和低、中、高3个剂量实验组的心肌IL-10水平分别为(0. 15±0. 02),(0. 68±0. 08),(0. 53±0. 06),(0. 42±0. 04)和(0. 24±0. 03)μg·L^(-1);这5组的IL-1β分别为(0. 19±0. 04),(1. 89±0. 22),(1. 32±0. 19),(1. 09±0. 15)和(0. 65±0. 09)μg·L^(-1);这5组的TNF-α分别为(0. 22±0. 03),(1. 48±0. 22),(0. 96±0. 16),(0. 72±0. 13)和(0. 53±0. 09)μg·L^(-1);这5组的的心肌梗死面积百分比分别为(8. 20±1. 25)%,(65. 40±9. 34)%,(48. 90±6. 21)%,(35. 60±4. 50)%和(26. 40±3. 20)%;模型组与假手术组相比,或低、中、高剂量3个实验组与模型组相比,上述指标的差异均有统计学意义(P <0. 05,P <0. 01)。结论地尔硫■预处理可通过抑制炎症反应从而对MIRI心脏具有保护作用。

Objective To observe the protective effect and mechanism of diltiazem on myocardial ischemia reperfusion injury(MIRI)in rat.Methods Sprague-Dawley rats were divided into 5 groups:Sham operation group,model group,and low,medium and high dose experimental groups.Rats in the low,medium and high dose experimental groups received intraperitoneal injection of diltiazem 50,100 and 200 mg·kg-1 before the model preparation,respectively;while the rats in sham operation group and model group were treated with 0.9%NaCl.Rats in model and experimental groups were ligated left anterior descending coronary artery for 30 and 40 min reperfusion,while without ligating the coronary artery in sham group.The levels of interleukin-10(IL-10),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)levels were determined by enzyme-linked immunosorbent assay.The percentage of myocardial infarction area was counted by Image J analysis system.Results The IL-10 levels of myocardial in sham operation group,model group,and low,medium,high dose experimental groups were(0.15±0.02),(0.68±0.08),(0.53±0.06),(0.42±0.04)and(0.24±0.03)μg·L-1;IL-1βlevels in the 5 groups were(0.19±0.04),(1.89±0.22),(1.32±0.19),(1.09±0.15)and(0.65±0.09)μg·L-1;TNF-αlevels in the 5 groups were(0.22±0.03),(1.48±0.22),(0.96±0.16),(0.72±0.13)and(0.53±0.09)μg·L-1;the percentages of myocardial infarction area in the 5 groups were(8.20±1.25)%,(65.40±9.34)%,(48.90±6.21)%,(35.60±4.50)%and(26.40±3.20)%,respectively;comparison between model group and sham operation group,and comparison between experimental groups and model group,the difference of the factors were significantly(P<0.05,P<0.01).Conclusion Diltiazem pretreatment can protect the heart from MIRI by inhibiting the inflammatory response.