脓毒血症大鼠甲状腺素替代治疗研究

A study of thyroxine replacement therapy in rats with sepsis

目的探讨脓毒血症大鼠甲状腺素替代治疗的预后及细胞超微结构的改变。方法清洁级SD健康雄性大鼠40只,体质量180~220 g。采用随机数字表法将大鼠分为脓毒血症组(S组)及甲状腺素替代治疗组(T组),每组各20只。大鼠均采用盲肠结扎穿孔术建立脓毒血症模型。T组大鼠分别在模型建立后0、24、48、72 h皮下注射左甲状腺素钠(10μg/100 g),S组给予同等剂量生理盐水。两组大鼠分别在术前、模型建立后24、48、72 h采血1.5 ml;然后,皮下注射生理盐1.5 ml/100 g补充失血;血液标本离心后,取血清用于检测甲功指标[游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)]及白细胞介素-6(IL-6)。观察两组大鼠96 h存活率。幸存大鼠处死后取甲状腺组织标本,用于超微结构观察。结果模型建立后24、48、72 h,S组、T组大鼠的FT3水平均低于本组术前(P<0.05),且T组各时间点FT3水平均低于S组(P<0.01);S组大鼠FT4水平低于术前,T组FT4水平高于本组术前及S组(P<0.05);T组TSH水平低于本组术前及S组(P<0.05),S组TSH水平与术前比较,差异无统计学意义(P>0.05)。模型建立后24、48、72 h,两组IL-6水平均高于各组术前,且24、48 h时间点均高于72 h(P<0.05),但两组间IL-6水平比较,差异无统计学意义(P>0.05)。两组大鼠24、48、72 h时间点的FT3、FT4、TSH水平组内比较,差异均无统计学意义(P>0.05);24、48 h时间点IL-6水平高于72 h(P<0.05)。T组大鼠96 h存活率高于S组(P<0.05)。电镜下,S组及T组大鼠甲状腺滤泡上皮细胞均出现不同程度胞核固缩、胞质溶解、胞膜破裂,但T组甲状腺滤泡结构破坏相对轻微。结论甲状腺素替代治疗可以增加盲肠结扎穿孔术制脓毒血症大鼠96 h内存活率,电子显微镜下可见甲状腺滤泡结构破坏相对减轻。

Objective To investigate the prognosis of septic rats for thyroxine replacement therapy and the change of ultra- structure in thyroid tissue. Methods A total of 40 pathogen-free male rats weighing 180 to 220 g were selected. Rats were randomly divided into the sepsis group （Group S）and thyroxine replacement therapy group（ Group T）, with 20 rats in each group. All rats were induced to septic modal by cecal ligation and puncture（CLP）. The rats in Group T were administrated L-thyroxine（ 10 μg/100 g）by hypodermic injection per time in 0 hour,24 hours,48 hours and 72 hours after the CLP. The rats in Group S were given the same dose normal saline. All rats were taken each 1.5 ml blood before CLP, 24 hours, 48 hours and 72 hours after CLP. After each blood collection, rats were taken normal saline（ 10 μg/100 g）for blood loss re- plenished. After centrifugation, blood samples were used for detection of thyroid hormones （ FT3 , FT4 and TSH） and interleu- kin-6（IL-6）. The rats＇ survival rate within 96 hours after CLP was recorded. The survival rats were executed and taken the thyroid tissue for observation of uhrastructure. Results After model establishment in 24 hours,48 hours and 72 hours, the FT3 levels in Group S and Group T were lower（P 〈0.05） ,and the FT3 level in Group T was lower than those at each time point in Group S （P 〈 0. 01 ）. The FT4 level in Group S was lower than that before surgery, and the FT4 level in Group T was higher than that before surgery and in Group S（ P 〈 0.05 ）. The TSH level in Group T was lower than that before surgery and in Group S（P 〈 0. 05）. After model establishment in 24 hours,48 hours and 72 hours, the IL-6 levels in both groups were higher than those before surgery, and the level at 24 hours and 48 hours were higher than that in 72 hours;the IL-6 levels between the both groups had no statistical significance（ P 〉 0. 05 ）. The levels of FT3, FF4 and TSH at 24 hours,48 hours and 72 hours had no statistical significance （P 〉 0.05 ）. IL-6 levels at 24 hours and 48 hours were higher than that at 72 hours （P 〈 0.05 ）. The survival rate in Group T was higher than that in Group S （P 〈 0. 05 ）. Under electron microscope, a series of pathological changes were found in thyroid follicular epithelial cells, such as the nucleus became smaller and showed pyknosis, cytoplasm was replaced by a lot of vacuole, the cell membrane broke, and the thyroid follicle in Group T was more complete than that in Group S. Conclusion Thyroxine replacement therapy can raise the survival rate of septic rat within 96 hours after CLP, and under electron microscopy, the structural damage of the thyroid follicle is reduced.