Severity of sepsis-induced acute kidney injury in a novel mouse model is age dep
Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent*Objective: Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories.
Design: Experimental animal investigation.
Setting: University research laboratory.
Subjects: Young (12–14 wks), aged (46–48 wks), and old (70–72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively.
Interventions: Uterine ligation and inoculation with 103 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection.
Measurements and Main Results: All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43%) compared to aged (23%) or young (9%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx− concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean ± sem; controls 0.18 ± 0.03 mg/dL, young 0.28 ± 0.03 mg/dL, aged 0.38 ± 0.05 mg/dL, and old 0.44 ± 0.06 mg/dL).
Conclusion: The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.
出处：(Crit Care Med 2012; 40:2638–2646)
Key Words: acute kidney injury; ageing; in vivo imaging; mouse; sepsis; uterus
Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent*
在新型小鼠模型中发现脓毒症诱导的急性肾功能损伤严重程度与年龄有关
目的：尽管有深入研究，但是因脓毒症诱发急性肾损伤病人的死亡率相当高，特别是在老年人中。目前的脓毒症模型很难再次模拟出AKI。本研究目的是通过结扎输尿管和接种细菌，制造出一种新型的模拟临床脓毒症诱导AKI 小鼠模型。另外，在3种不同年龄段的模型中研究年龄与脓毒症和脓毒症诱导的AKI的严重程度的关系。
对象：青年(12–14周龄)，中年(46–48周龄)和老年(70–72周龄) C57BL/6雌性小鼠分别作为青春期，成年绝经前和老年绝经后对象。
干预：结扎输尿管并接种103CFU的大肠埃希菌或盐水，用发光大肠埃希菌染色的体外影像证实感染过程。
测量和主要结果所有小鼠在感染后48小时形成大肠埃希菌脓毒症，在老年组的死亡率(43%)高于中年组(23%)和青年组(9%)。感染小鼠的血清或血浆的细胞因子，趋化因子（肿瘤坏死因子，白介素-6，角化蛋白来源的趋化因子，单核细胞趋化蛋白-1和白介素-10）和NOx−浓度比对照组高。肾组织学确认AKI。在48小时时血清肌酐浓度随年龄增加（对照组0.18 ± 0.03 mg/dL，中年组0.38 ± 0.05 mg/dL，老年组0.44 ± 0.06 mg/dL）。
结论输尿管结扎和接种造成脓毒症诱导AKI 模型可以形成真正的感染灶，并表现出与人类AKI相似的脓毒症AKI年龄依赖严重性。
页:
[1]