血管紧张素(1-7)对小鼠肢体缺血再灌注所致肾损伤的改善作用及其机制

doi:10.13481/j.1671-587X.20210403

Abstract

Abstract: Objective

To explore the effect of angiotensin （1-7）［Ang-（1-7）］ on renal injury and inflammation in the limb ischemia-reperfusion （LIR） mice by detecting the level of Ang-（1-7） in kidey tissue and serum and the expression levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α） and Mas receptor protein in kindey tissue of the LIR mice pretreated with Ang-（1-7）.

Methods

Thirty 10-week-old C57BL/6 mice were randomly divided into control group， LIR group， and LIR+Ang-（1-7） group， with 10 mice in each group. The mice in LIR group and LIR+Ang-（1-7） group were subjected to 2 h of ischemia and 4 h of reperfusion to establish the mouse LIR models. The mice in LIR+Ang-（1-7） group were treated Ang-（1-7）（24 μg·kg^－1·h^－1） for two weeks before LIR by placing subcutaneous osmotic pump. The mice in LIR group were treated the same amount of normal saline for two weeks before LIR by placed subcutaneous osmotic pump. Automatic biochemical analyzer was used to determine the levels of serum creatinine （SCr） and urea nitrogen （BUN） of the mice； HE staining was used to observe the pathomorphology of kidney tissue of the mice， and renal tubular pathological score was performed. Enzyme linked immunosorbent assay （ELISA） was used to determine the Ang-（1-7） levels in kidney tissue and serum of the mice. Immunohistochemical staining and Western blotting methods were used to detect the expression， distribution and the expression levels of NF-κB，TNF-α and Mas receptor proteins in the mouse kidney tissue.

Results

Compared with control group， the levels of serum SCr and BUN of the mice in LIR group were increased significantly （P<0.05）， and the obvious pathological damages such as hyperemia， renal tubular dilation， edema， necrosis， and inflammatory cell infiltration were observed in the kidney tissue； the pathological injury score of kidney tissue was increased（P<0.05）； the Ang-（1-7） levels in kidney tissue and serum of the mice were decreased significantly （P<0.05）， and the expression levels of NF-κB， TNF-α and Mas receptor proteins were increased significantly （P<0.05）. Compared with LIR group， the levels of serum SCr and BUN of the mice in LIR+Ang-（1-7） group were decreased significantly （P<0.05），and the kidney congestion and other damages were significantly reduced；the pathological injury score of kindey tissue was decreased（P<0.05）； the Ang-（1-7） levels in kidney tissue and serum of the mice were increased significantly （P<0.05）； the expression levels of NF-κB and TNF-α proteins were decreased （P<0.05）， and the expression level of Mas receptor protein in kidney tissue of the mice in LIR+Ang-（1-7） group was increased significantly （P<0.05）.

Conclusion

Mouse LIR can induce the distal kidney damage， and Ang-（1-7） may reduce the expression levels of NF-κB and TNF-α proteins in kidney tissue to improve the kidney damage caused by mouse LIR.

Key words: ischemia-reperfusion, acute kidney injury, renin-angiotensin system, inflammation

CLC Number:

R363

Liyan ZHU,Yaoming WANG,Zheng QIN,Huanhuan ZHAO,Zengying WANG,Xiuhong YANG. Improvement effect of angiotensin(1-7) on kidney injury induced by limb ischemia-reperfusion in mice and its mechanism[J].Journal of Jilin University(Medicine Edition), 2021, 47(4): 834-841.

Figures/Tables 6

Tab. 1

Fig. 1

Tab. 2

Fig. 2

Tab. 3

Fig. 3

References 24

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Group	Scr [c_B/(μmol·L^－1)]	BUN [c_B/(mmol·L^－1)]	Pathological injury score
Control	19.92±1.96	7.95±2.06	14.67±3.54
LIR	30.35±5.09^*	13.36±2.45^*	55.20±9.13^*
LIR+Ang-(1-7)	24.94±2.72^△	9.91±1.69^△	36.80±4.02^△
^*P<0.05 vs control group;^△P<0.05 vs LIR group.

Group	Ang-(1-7)
Group	Kindey tissue [w_B/(ng·g^－1)]	Serum [c_B/(mmol·L^－1)]
Control	14.05±1.44	1.76±0.13
LIR	11.99±1.29^*	1.39±0.29^*
LIR+Ang-(1-7)	16.53±3.15^△	2.10±0.29^△
^*P<0.05 vs control group; ^△P<0.05 vs LIR group.

Group	TNF-α	NF-κB	Mas receptor
Control	0.08±0.02	0.10±0.01	0.16±0.01
LIR	0.21±0.03^*	0.22±0.02^*	0.21±0.01^*
LIR+Ang-(1-7)	0.13±0.02^△	0.19±0.02^△	0.28±0.01^△
^*P<0.05 vs control group;^△P<0.05 vs LIR group.

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Improvement effect of angiotensin(1-7) on kidney injury induced by limb ischemia-reperfusion in mice and its mechanism

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