Time-course changes of remote apoptosis and necroptosis of pulmonary cells induced by acute kidney injury in mice

Ziheng YANG; Zhigang QIN; Jieyu LI; Xiangfeng LIU; Yirong LI; Peng LI; Jianteng GU

doi:10.16016/j.2097-0927.202206014

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Time-course changes of remote apoptosis and necroptosis of pulmonary cells induced by acute kidney injury in mice

Basic Medicine | 更新时间：2026-01-09

- Time-course changes of remote apoptosis and necroptosis of pulmonary cells induced by acute kidney injury in mice
- Journal of Army Medical University Vol. 44, Issue 20, Pages: 2098-2104(2022)
- 作者机构：
  
  1.400038 重庆, 陆军军医大学(第三军医大学)：第一附属医院麻醉科
  2.400038 重庆, 陆军军医大学(第三军医大学)：药学与检验医学系生药学与中药学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81772050);the Excellent Talents Foundation of Army Medical University(XZ2019-505-028)
- DOI：10.16016/j.2097-0927.202206014
  CLC： R363.23;R563.02;R692.01
- Received：03 June 2022，
  
  Revised：2022-08-22，
  
  Published：30 October 2022
- 稿件说明：
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Ziheng YANG, Zhigang QIN, Jieyu LI, et al. Time-course changes of remote apoptosis and necroptosis of pulmonary cells induced by acute kidney injury in mice[J]. Journal of Army Medical University, 2022, 44(20): 2098-2104.
DOI：

Ziheng YANG, Zhigang QIN, Jieyu LI, et al. Time-course changes of remote apoptosis and necroptosis of pulmonary cells induced by acute kidney injury in mice[J]. Journal of Army Medical University, 2022, 44(20): 2098-2104. DOI： 10.16016/j.2097-0927.202206014.

摘要

目的

探索小鼠急性肾损伤致远端肺损伤过程中，肺部细胞凋亡和程序性坏死随时间的变化规律。

方法

30只8周龄雄性C57BL/6J小鼠(体质量20~22 g)按照随机数字表法平均分为6组(

=5)：假手术(Sham)组，行开腹关腹手术；肾缺血再灌注(RI/r)6、12、24、36、48 h组，双肾夹闭缺血50 min后，再分别灌注6、12、24、36、48 h。HE染色评估肺组织损伤；专用试剂盒测定血清中肌酐(creatinine，Cr)及尿素氮(blood urea nitrogen，BUN)浓度；TUNEL检测肺细胞凋亡；免疫荧光染色检测磷酸化混合系列蛋白激酶样结构域蛋白(phosphorylation mixed lineage kinase domain like protein，p-MLKL)；Western Blot检测磷酸化受体相互作用蛋白激酶1(phosphorylation receptor-interacting protein 1，p-RIP1)、p-MLKL和cleaved Caspase-3。

结果

肾缺血再灌注后24 h内，小鼠血清Cr、BUN水平与肺组织HE染色病理损伤评分随时间延长逐渐升高，肾功能损伤程度与肺损伤程度呈正相关；肺组织凋亡阳性细胞和cleaved Caspase-3表达水平随时间延长逐渐增多。与Sham组比较，RI/r12、24、36、48 h组小鼠肺组织凋亡细胞显著增多(

0.05)，RI/r24、36、48 h组cleaved Caspase-3表达水平显著增高(

0.05)；p-MLKL和p-RIP1表达随时间延长逐渐增多，再灌注36 h时p-MLKL达到峰值之后下降。

结论

肾缺血再灌注48 h内，肺损伤逐渐加重，肺细胞凋亡持续增加，程序性坏死于36 h达峰后减少。

Abstract

Objective

To explore the change patterns of apoptosis and necroptosis in lung cells over time during acute kidney injury-induced distal lung injury.

Methods

Thirty male C57BL/6J mice (8 weeks old) were randomly divided into Sham operation group (undergoing laparotomy only)

and renal ischemia-reperfusion groups (RI/r groups

bilateral kidney ischemia for 50 min followed by reperfusion for 6

36 and 48 h respectively)

with 5 animals in each group. HE staining was performed to assess lung tissue injury. The serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were determined with corresponding reagent kits. The lung cell apoptosis was detected by TUNEL. Immunofluorescence staining was used to investigate the expression of phosphorylation mixed lineage kinase domain like protein (p-MLKL)

and Western blotting was employed to measure the expression levels of phosphorylation receptor-interacting protein 1 (p-RIP1)

p-MLKL and cleaved Caspase-3.

Results

Within 24 h after renal I/R injury

the serum levels of Cr and BUN and pulmonary pathological injury score were increased in a time-dependent manner

and the severity of renal injury was positively correlated with that of lung injury. The number of apoptotic cells and the expression level of cleaved Caspase-3 in the lung were raised gradually with the elapse of time. Compared with the Sham operation group

the number of apoptotic cells was elevated in the RI/r12

36 and 48 h groups (

0.05)

and the expression of cleaved Caspase-3 was notably up-regulated in the RI/r 24

36 and 48 h groups (

0.05). The expression levels of p-MLKL and p-RIP1 were increased time-dependently

and the p-MLKL level was then declined gradually after reaching a peak at 36 h after reperfusion.

Conclusion

Within 48 h after renal I/R injury

lung injury is exacerbated gradually. The number of apoptotic lung cells continues to increase

but that of necroptosis is in a trend of decrease after reaching a peak at 36 h.

关键词

Keywords

references

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