不同剂量氢化可的松对脓毒性休克早期大鼠凝血功能影响的实验研究

Effects of different doses of hydrocortisone on the disorder of coagulation in rats at early stage of septic shock

该论文说明不同剂量HC对脓毒性休克早期大鼠凝血功能的影响不同。小剂量可能有利于改善脓毒性休克早期大鼠的凝血紊乱，保护微血管内皮细胞；大、中剂量对脓毒性休克早期大鼠凝血紊乱的改善并不显著，大剂量HC甚至在某些指标上会加重损伤，可能促进高凝状态发生；中剂量HC作用介于两者之问。该结果为临床使用GC治疗脓毒性休克提供了一定的实验依据。

Objective To evaluate the effects of three different doses of hydrocortisone （HC） on some aspects of coagulation and fibrinolysis in severe sepsis rats, and try to provide some evidence for the medical workers to choose more reasonable doses of glucocorticoid （GC） in the treatment of sepsis. Methods The model of early septic shock accompanied by the disorder of coagulation in rats was induced by bolus injection of lipopolysaccharide （LPS） at 25 mg/kg through right femoral vein. 40 male Wistar rats were randomly divided into the following 5 groups： normal control （LPS and HC were substituted by same volume of normal saline）, shock group （HC was substituted by same volume of normal saline）, high-dose HC （HD group, HC100 mg/kg）, middleose HC （MD group, HC 50 mg/kg） and low-dose HC （LD group, HC 5 mg/kg）. Four hours after the HC treatment, the specimens were collected for the count of blood platelet （PLT）, the activity of antithrombin m （AT m）, the content of D-Dimer and yon Willebrand factor （vWF）.We also investigated the expression of tissue factor （TF） on the macrophages in liver using immunohistochemical method, the changes of aminopherase, and histopathologic changes of ultramicrostructure of endothelial cells of hepatic sinusoids by electron microscopy. Results 1 ）The count of PLT and the activities of AT m in LPS group were significantly lower than that in normal control group, P〈0.05. After given HC, the count of PLT in the three HC groups all increased significantly, P〈0.05. However, the activities of AT m increased significantly only in LD group, P〈0.05. The level of D-Dimer and vWF in shock group were significantly higher than that in normal control group. Although both of them reduced in the HC groups, the difference was significant only between LD and shock groups, P〈0.05. And there was no significant difference between LD and normal control groups, P〈0.05.2）The expression of TF in liver and the level of aminotransferase： Light microscopy examination indicated the degree of impairment of shock group are much more severe than normal control group, and the injury of HD group are similar to that of shock group. The injury was attenuated obviously in LD group. There was very weak staining of TF in macrophages of liver in normal control group. The expression of TF in shock group was significantly in- creased compared with normal group, P〈0.05. Among the HC groups, the expression of TF was significantly reduced only in LD group, P〈0.05. The expression of TF in HD group even increased more than in shock group, P〉0.05. The levels of aminotransferases were much higher in LPS group than in normal control group, P〈0.05. The levels of alanine aminotransferase （ALT） were reduced in HC groups, and the reduction in MD and LD groups was significant when compared with shock group, P〈0.05. There was no significant difference in ALT level between LD and nomal control group. Among three HC groups, the levels of aspartare aminotransferase （AST） were significantly reduced only in LD group, P〈0.05. The difference was also significant in AST levels between LD and the other two groups, P〈0.05.3）The uhramicrostructure of Sinusoidal endothelial cells in rat liver： We could find edema and decreased density in cytoplasm, swelling of organelles and widen intercellular space in shock group by transmission electron microscopy. The changes of HD group were similar to that of shock group. The uhramicrostructure of endothelium in LD group was improved significantly, and was similar to those of normal control group. The degree of impairment in MD group was between HD and LD groups. Conclusions Different dosese of HC has different effects on coagulation and fibrinolysis in early stage of septic shock rats. Low dose of HC may ameliorate the disorder of coagulation, protect vascular endothelial cells in early septic shock rats. High-dose and middle-dose of HC had no significant improvements in the disorder of coagulation. High dose of HC may aggravate the injury on some aspects and result in hypercoagulabale state. The effect of middle dose HC is between LD and HD groups.