乌司他丁和胸腺肽α1联合治疗严重脓毒症的组织病理学观察

Ulinastatin combined with thymosin α1 for treatment of severe sepsis: a histopathological observation in rats

目的通过组织病理学观察联合应用乌司他丁和胸腺肽α1治疗严重脓毒症的效果。方法采用经典大鼠CLP脓毒症模型,全部动物随机分为对照组、联合治疗组(乌司他丁+胸腺肽α1)、乌司他丁治疗组和胸腺肽α1治疗组。制模成功后分别于6、24、48和72 h经尾静脉或皮下注射给药,记录每天死亡数。制模后24、48、72和96 h处死动物,留取心、肝、脾、肺、肾、小肠标本,以光镜进行病理学检查,脾脏标本行凋亡检测。结果联合治疗组死亡率显著降低(P=0.0325);组织病理学显示,对照组各脏器损害最严重,单药组其次,联合用药组最轻;此外,对照组脾脏细胞大量凋亡,联合用药组凋亡程度显著下降[(47.4±10.9)%vs(39.3±11.4)%,P=0.0000]。结论乌司他丁和胸腺肽α1联合用药可以显著减轻脓毒症大鼠脏器损害,抑制脾脏细胞凋亡,提高脓毒症大鼠存活率。

Objective To evaluate the therapeutic effect of ulinastatin combined with thymosin α1 in the treatment of severe sepsis in rats. Methods Normal Wistar rats were subject to cecal ligation and puncture （CLP） to establish models of severe sepsis. The rats were then randomized into 4 groups for treatment with saline （control）, ulinastatin, thymosin α1, or the combination of the latter two injected through the caudal vein or subcutaqneously at 6, 24, 48 and 72 h after modeling. The mortality rate was recorded daily and the rats were executed at 24, 48, 72 and 96 h after CLP to harvest the heart, liver, spleen, lung, kidney and small intestines for pathological examination. The spleen of the rats were taken for detection of apoptosis of the spleen cells. Results The mortality rate of the septic rats in the combined treatment group was decreased significantly （P= 0.0325）. The control group showed the most severe organ damage, which was moderate in single drug treatment group and the mildest in combined treatment group. Obvious spleen cell apoptosis was found in the control group, and was significantly ameliorated in the combined treatment group [（47.4±10.9）% vs （39.3±11.4）%, P=0.00001. Conclusion Combined treatment with ulinastatin and thymosin α1 can significantly improve the prognosis and ameliorate organ damage and spleen cell apoptosis in rats with sever sepsis.