Inhibition Of Renal Injury

急性肾功能衰竭具有较高的发病率和病死率。我们已经开发了一套新的脓毒症诱导的ARF模型，该模型采用盲肠结扎穿刺法对老年小鼠进行液体和抗生素治疗。我们得到了肌酐的增加和肾脏组织学的轻微变化-类似于人类ARF-以及其他器官(肺、肝、肌肉等)损伤的明显证据。这些模型非常令人兴奋，因为小鼠被用液体和抗生素治疗，就像人类感染败血症一样。我们现在正在研究损伤的病理生理学，筛选药物，并研究它们的作用机制。 我们已经使用该模型来筛选抑制肾脏和多器官损伤的药物。我们已经发现了三种药物(丙酸乙酯、吡非尼酮、RDT2和RDT3)可以抑制肾损伤，即使在脓毒症诱导后8-12小时首次使用也是如此。我们发现阻断TNFa或TRL2受体对ARF没有影响。然而，我们可以使用敲除系统在不改变脓毒症的情况下阻止肾脏损伤。 我们还进行了微阵列实验，以寻找新的药物靶点和生物标记物，并进行了其他研究，以探讨疾病的机制。

Acute renal failure has a high morbidity and mortality. We have finished developing a set of new model of sepsis-induced ARF that employ cecal ligation puncture in elderly mice treated with fluids and antibiotics. We get increases in creatinine and modest changes in renal histology - similar to human ARF - along with clear evidence of injury in other organs (lung, liver, muscle, etc). These models are very exciting because the mice are treated with fluids and antibiotics, as occurs to humans with sepsis. We are now studying the pathophysiology of injury, screening drugs, and studying their mechanisms of action. We have used the model to screen for drugs that inhibit renal and multiorgan damage. We have found three drugs (Ethyl pyurvate, Pirfenidone, RDT2, and RDT3) that inhibit renal injury, even when first started 8-12 hours after induction of sepsis. We found that blocking TNFa or TRL2 receptors has no effect on ARF. However, we can block renal injury, without altering sepsis using a knock-out system. We have also performed microarray experiments to search for new drug targets and biomarkers, and additional studies that investigate the mechanism of disease.