乌司他丁心血管保护作用的实验研究

Experimental study for protective effects of ulinastatin from cardiovascular disease

目的：探讨蛋白酶抑制剂乌司他丁对心肌梗塞后心肌的保护作用及其可能机制。方法：选取3~5月龄日本大耳白兔30只,结扎兔前降支制作心肌梗塞模型,随机均分为对照组（予生理盐水）、常规治疗组（予硝酸甘油等常规治疗）、乌司他丁组（在常规治疗基础上给予乌司他丁治疗）。模型制作前、后4周行心脏超声检查,以红四氮唑（TTC）染色评价梗塞面积,流式细胞仪测定细胞凋亡,测定血浆肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6等炎症因子水平。结果：治疗后,乌司他丁组较常规治疗组和对照组左室射血分数明显提高[（56.91±2.04）%∶（53.22±2.13）%∶（32.49±1.29）%]、梗塞面积显著减小[（21.82±3.12）%∶（24.61±1.24）%∶（29.73±2.11）%]、细胞凋亡明显减少[（4.98±0.58）%∶（6.75±0.51）%∶（9.64±0.23）%],P均〈0.05;心肌梗塞后1周内TNF-α水平[（331.4±13.6）ng/L∶（391.1±16.9）ng/L∶（411.5±10.3）ng/L]、IL-6水平[（312.2±25.7）ng/L∶（359.4±30.3）ng/L∶（409.6±9.1）ng/L]明显降低（P均〈0.05）,两周后三组炎症因子水平无明显差异（P均〉0.05）。结论：乌司他丁具有心肌保护作用,机制可能与抑制梗塞面积扩大、细胞凋亡及抗炎作用有关。

Objective： To explore protective effects of proteinase inhibitor-ulinastatin from cardiovascular disease（myocardial infarction） and its possible mechanism.Methods： A total of 30 Japanese big-ear rabbits（3~5 months old） were chosen.Anterior descending branch of coronary of rabbit was ligated to make model of myocardial infarction.Then the rabbits were randomly and equally divided into control group（received saline）,routine treatment group（received routine treatment as nitroglycerin etc.） and ulinastatin group（received ulinastatin based on routine treatment）.The patients received echocardiogram examination before and four weeks after treatment.Tetrazolium chloride staining was used to evaluate infarct size,flow cytometry was used to measure apoptosis and enzyme liked immunosorbent assay（ELISA）was used to measure plasma levels of tumor necrosis factor-a（TNF-a） and interleukin-6（IL-6）.Results： After treatment,for ulinastatin group left ventricular ejection fraction significantly improved [（56.91±2.04）% vs.（53.22±2.13）% vs.（32.49±1.29）%],infarct size significantly decreased [（21.82±3.12）% vs.（24.61±1.24）% vs.（29.73±2.11）%],apoptosis significantly decreased [（4.98±0.58）% vs.（6.75±0.51）% vs.（9.64±0.23）%];levels of TNF-α [（331.4±13.6） ng/L vs.（391.1±16.9） ng/L vs.（411.5±10.3） ng/L] and IL-6 [（312.2±25.7） ng/L vs.（359.4±30.3） ng/L vs.（409.6±9.1） ng/L] significantly decreased within one week after myocardial infarction compared with routine treatment group and control group（P0.05 all）.Levels of inflammatory factors in the three groups showed no significant difference after two weeks（P0.05 all）.Conclusion： Ulinastatin possesses protective effect on myocardium,and its mechanism may be related to inhibition of expansion of infarct size,apoptosis and anti-inflammation.