Liu Xin, Wang Ning, Wei Guo, Fan Shijun, Lu Yongling, Zhu Yuanfeng, Chen Qian, Huang Min, Zhou Hong, Zheng Jiang
Medical Research Center, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, PR China.
Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing, 400038, PR China.
Int Immunopharmacol. 2016 Mar;32:66-75. doi: 10.1016/j.intimp.2015.12.041. Epub 2016 Jan 21.
Sepsis is the leading cause of death for critical ill patients and an essential focus in immunopharmacological research. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study. However, this animal model is easily affected by variability problems and dramatically affects pharmacological evaluation of anti-sepsis therapies, which requires standardized procedures and stable outcomes. Herein, the traditional syringe needle based puncture method was used as the major unstable factor for CLP models. Syringe needles created varied mortality in parallel experimental groups of CLP rats; they were inconsistent for severity control as mortality in CLP rats was not correlated with change in punctures, ligation lengths, or needle sizes. Moreover, the use of drainage tubes or strips, which was supposed to strengthen drainage stability, also failed to improve consistency of traditional syringe needles. To solve the consistency problem, an improved design of CLP surgery by puncture with newly-developed three-edged needles was described herein. In contrast to traditional syringe needles, these three-edged needles ensured more stable outcomes in repetitive groups. Furthermore, increased severity was found to be consistent with the enlarged needle size, as shown by the elevated mortality, increased proinflammatory cytokines, abnormal coagulation, worsen acidosis and more severe acute lung injury. In conclusion, application of the newly-developed three-edged needles provides a simple and feasible method to improve stability when conducting CLP surgery, which is significant for pharmacological studies on sepsis.
脓毒症是危重症患者的主要死因，也是免疫药理学研究的重要焦点。盲肠结扎穿孔（CLP）模型被视为脓毒症研究的金标准模型。然而，该动物模型容易受到变异性问题的影响，极大地影响了抗脓毒症疗法的药理学评估，这就需要标准化的程序和稳定的结果。在此，基于传统注射器针头的穿刺方法被认为是CLP模型的主要不稳定因素。注射器针头在CLP大鼠的平行实验组中造成了不同的死亡率；在控制严重程度方面并不一致，因为CLP大鼠的死亡率与穿刺次数、结扎长度或针头尺寸的变化无关。此外，使用引流管或引流条本应增强引流稳定性，但也未能提高传统注射器针头的一致性。为了解决一致性问题，本文描述了一种通过使用新开发的三棱针进行穿刺来改进CLP手术的设计。与传统注射器针头相比，这些三棱针在重复实验中确保了更稳定的结果。此外，发现严重程度的增加与针头尺寸的增大一致，表现为死亡率升高、促炎细胞因子增加、凝血异常、酸中毒加重和更严重的急性肺损伤。总之，应用新开发的三棱针为进行CLP手术时提高稳定性提供了一种简单可行的方法，这对脓毒症的药理学研究具有重要意义。
