水蛭素对脓毒症大鼠凝血功能障碍影响的实验研究

Experimental study on the effect of hirudin on coagulation disorders in septic rats

目的探讨水蛭素对脓毒症大鼠凝血功能障碍的影响。方法将75只大鼠随机分为假手术组、模型组和水蛭素组。除假手术组外,其余各组以盲肠结扎穿孔的方法建立脓毒症大鼠模型。术后取大鼠静脉血样本,检测各组及各时间点的常规凝血功能指标和凝血与血小板功能分析仪参数,取大鼠肺和回肠组织进行病理切片观察,采用方差分析各组的凝血指标,并观察各组大鼠48h的生存率。结果术后48h,假手术组、模型组和水蛭素组大鼠的存活率分别为100%、10%和50%。术后6h:水蛭素组大鼠的血小板计数较模型组显著降低;模型组大鼠的活化凝血时间(activated clotting time,ACT)较假手术组、水蛭素组明显缩短(F=7.190,P<0.05);模型组、水蛭素组大鼠的凝血速率(clot rate,CR)值较假手术组显著上升(F=4.549,P<0.05)。术后12h:模型组和水蛭素组大鼠的血小板计数较假手术组明显降低(F=4.780,P<0.05);模型组大鼠的ACT值和CR值明显延长(F=4.863、12.923,P<0.05);水蛭素组大鼠的CR值上升;模型组、水蛭素组大鼠的CR值较假手术组显著上升(F=11.791,P<0.05)。术后24h:模型组大鼠的ACT值和CR值明显延长(F=4.863、12.923,P<0.05);水蛭素组大鼠的血小板计数较模型组显著升高(F=13.574,P<0.05);模型组、水蛭素组大鼠的CR值较假手术组显著上升,而水蛭素组大鼠的CR值较模型组明显下降(F=25.854,P<0.05)。水蛭素组大鼠肺泡腔减少数量、炎症细胞浸润及微血管内微血栓形成较模型组大鼠明显减轻;肠粘膜上皮坏死、间质水肿及炎症细胞浸润情况较模型组大鼠显著减轻。结论水蛭素能上调大鼠的血小板数量,调节凝血因子活性和纤维蛋白原功能,保护脓毒症大鼠的肺肠器官功能,降低其死亡率。

Objective To explore the effects of hirudin on coagulation disorders in septic rats.Methods Seventy-five rats were randomly divided into sham operation,model,and hirudin groups.Except for the sham surgery group,septic rat models were established in the remaining groups using cecal ligation and perforation.Venous blood samples were collected postoperatively from the rats to test routine coagulation function indicators and coagulation and platelet function analyzer parameters for each group and at each time point.Sections of rat lung and ileum tissues were examined pathologically.Variance analysis was used to analyze coagulation indicators in each group.Survival rates at 48 hours were observed for rats in all groups.Results Forty-eight hours after operation,rat survival rates in the sham operation,model,and hirudin groups were 100%,10%,and 50%,respectively.At 6 hours post-operation,platelet(PLT)count of rats was significantly lower in the hirudin group compared to the model group.The activated clotting time(ACT)of rats was significantly shorter in the model group than in both the hirudin and sham operation groups(F=7.190,P<0.05).The coagulation rate(CR)of rats significantly increased in both the model and hirudin groups compared to the sham operation group(F=4.549,P<0.05).At 12 hours post-operation,PLT count of rats was significantly lower in both the model and hirudin groups than in the sham operation group(F=4.780,P<0.05).ACT value and CR value of rats were significantly longer in the model group(F=4.863,12.923,P<0.05).The CR value of rats increased significantly in the hirudin group.The CR value of rats in both the model group and hirudin group were significantly higher than those in the sham operation group(F=11.791,P<0.05).At 24 hours post-operation,ACT and CR value of rats were significantly longer in the model group(F=4.863,12.923,P<0.05).PLT count of rats was significantly higher in the hirudin group than in the model group(F=13.574,P<0.05).The CR value of rats in both the model group and hirudin group increased significantly compared to the sham operation group,but the CR value in the hirudin group decreased significantly compared to the model group(F=25.854,P<0.05).Compared to the model group of rats,the hirudin group showed a significant reduction in the number of alveolar cavities,inflammatory cell infiltration,and microvascular microthrombosis.Additionally,intestinal mucosal epithelial necrosis,interstitial edema,and inflammatory cell infiltration were significantly reduced in the hirudin group than the model group of rats.Conclusion Hirudin can increase platelet count of rats,adjust coagulation factor activity,and fibrinogen function,and protect organ function in septic rats,thereby reducing their mortality.