乌司他丁量效关系对心肌保护作用影响的实验研究

目的:探讨乌司他丁(UTI)量效关系对心肌保护作用的影响及其可能机制。方法:腹腔注射阿霉素制作大鼠扩张型心肌病动物模型,40只SD扩张型心肌病模型大鼠被随机均分为空白对照组(给予生理盐水)、低剂量组(UTI 10000U/kg)、中等剂量组(UTI 30000U/kg)、高剂量组(UTI 60000U/kg),连续给药2周,实验前后分别行心脏超声检查,测定左室内径、左室射血分数(LVEF),以黄嘌呤氧化酶法测定血浆超氧化物歧化酶(SOD)水平,氯胺T氧化法测定心肌局部组织羟脯氨酸(Hyp)含量,评估心肌间质纤维化程度。结果:与空白对照组、低和中等剂量组相比,高剂量组治疗后LVEF[(32.49±1.29)%、(53.22±2.13)%、(56.91±2.04)%比(62.61±2.37)%]、SOD水平[(4.06±0.71)U/ml、(5.25±0.18)U/ml、(5.79±0.69)U/ml比(6.96±0.77)U/ml]明显升高(P均<0.05);左室舒张末期内径[LVEDd,(1.53±0.13)mm、(1.21±0.02)mm、(1.21±0.09)mm比(1.01±0.01)mm]明显减小、心肌局部组织Hyp含量[(40.16±2.31)μg/mg、(34.24±1.98)μg/mg、(22.79±1.69)μg/mg比(19.84±1.47)μg/mg]明显降低(P均<0.05)。与空白对照组比较,UTI低、中、高剂量组左室收缩末期内径[LVESd,(1.23±0.02)mm、(0.98±0.04)mm、(0.98±0.12)mm比(0.99±0.03)mm]显著减小(P均<0.05)。结论:大剂量乌司他丁心肌保护作用更好,原因可能与抑制心室重塑、拮抗氧自由基有关。

Influence of dose-effect relationship of ulinastatin on myocardial protection

Objective： To explore influence of dose-effect relationship of ulinastatin （UTI） on myocardial protection and its possible mechanism. Methods： Rat model of dilated cardiomyopathy was established by intraperitoneal injec- tion of Adriamycin. A total of 40 SD rats with dilated cardiomyopathy were randomly and equally divided into blank control group （receivednormal saline）, UTI low dose group （received UTI 10000 U/kg）, UTI medium dose group （received UTI 30000 U/kg） and UTI high dose group （received UTI 60000 U/kg）, then they were treated for two weeks. Echocardiography was used to measure left ventricular diameter, left ventricular ejection fraction （LVEF） ; the xanthine oxidase method was used to measure plasma level of superoxide dismutase （SOD）, chloramine-T oxida- tion method was used to measure hydroxyproline （Hyp） concentration in partial tissue of myocardium to evaluate de- gree of myocardial interstitial fibrosis before and after experiment. Results： Compared with blank control, UTI low and medium dose group after treatment, there were significant increase in LVEF [ （32.49 ± 1.29） %, （53.22± 2.13）%, （56.91±2.04）% vs. （62.61±2.37）%] and SOD level [ （4.06±0.71） U/ml, （5.25±0.18） U/ml, （5.79 ±0.69） U/ml vs. （6.96 ± 0.77） U/ml], P〈0.05 all and significant decrease in left ventricular end-diastolic dimension [LVEDd, （1.53± 0.13） mm, （1.21 ± 0.02） mm, （1.21 ± 0.09） mm vs. （1.01 ±0.01） mm], and Hyp concentration [ （40.16±2.31） μg/mg, （34.24± 1.98） μg/mg, （22.79 ± 1.69） t~g/mg vs. （19.84±1.47） μg/mg] in partial tissue of myocardium in UTI high dose group （P〈0.05 all）. Compared with blank control, left ventricu-lar end-systolic dimension ELVESd, （1.23± 0.02） mm, （0. 98± 0.04） mm, （0.98 ±0. 12） mm vs. （0.99 ±0. 03） mm] significant decreased in UTI low, medium and high dose group after treatment （P〈0.05 all）. Conclusion： Large dose of ulinastatin possesses better myocardial protection effect, which may be related with inhibition of ven- tricular remodeling and antagonism of oxygen radical.