蛋白激酶Cβ抑制剂通过调节巨噬细胞表型对移植期间的肾缺血再灌注损伤的影响

doi:10.3969/j.issn.1006-5725.2025.01.004

Abstract

Abstract:

Objective To investigate whether PKCβ inhibitor can alleviate RIRI by regulating macrophage phenotype. Methods Rats in the renal ischemia?reperfusion injury （RIRI） model group underwent right nephrectomy followed by a 60?minute clamping of the left renal pedicle. In the experimental group （Inhibitor + RIRI）， PKCβ inhibitors were administered orally one day prior to surgery. All rats were euthanized 24 hours post?surgery for the collection of blood and left kidney samples. Renal function， tissue morphology， and the expression levels of renal tubular injury marker KIM?1， renal papilla injury marker RPA?1， macrophage subtype markers， and inflammatory factors were evaluated. Results PKCβ inhibitors alleviated renal ischemia?reperfusion injury in rats. PAS staining revealed marked tubular damage in kidney sections from the RIRI group， whereas kidney inflammatory cell infiltration and renal tubular injury scores were significantly reduced in the Inhibitor+RIRI group following PKCβ inhibitor treatment （all P < 0.05）. The expression levels of Cr， BUN， KIM?1， and RPA?1 were markedly elevated in the RIRI group compared to the Sham and Inhibitor + RIRI groups （all P < 0.05）. After PKCβ inhibitor intervention， the expression levels of Cr， BUN， KIM?1， and RPA?1 were significantly decreased in the Inhibitor + RIRI group relative to the RIRI group （all P < 0.05）. Protein expression levels of iNOS， IL?2， and CD197 in the kidney tissue of the RIRI group were significantly higher than those in the Sham and Inhibitor + RIRI groups （all P < 0.05）. Compared with the RIRI group， the protein expression levels of iNOS， IL?12， and CD197 were significantly reduced in the Inhibitor + RIRI group following PKC β inhibitor intervention （all P < 0.05）. Additionally， the protein expression levels of Dectin?1， ARG?1， and CD163 were significantly higher in the Inhibitor + RIRI group than in the RIRI and Sham groups after PKCβ inhibitor intervention （all P < 0.05）. Conclusions PKCβ inhibitors can mitigate renal dysfunction， renal tubular injury， and the expression of injury markers in the renal tubules and renal papilla following ischemia?reperfusion. Additionally， PKCβ inhibitors play a role in modulating macrophage subtypes by reducing M1 macrophages and promoting polarization to M2， which leads to a decrease in pro?inflammatory factors and an increase in anti?inflammatory factors， ultimately facilitating kidney repair.

Key words: renal ischemia?reperfusion injury, PKC β inhibitor, inflammatory factors, M1 macrophages, M2 macrophages

CLC Number:

R692

Chunyan LI,Ting XIAO,Bangcui WU,Yong CHEN,Mei TIAN. PKCβ inhibitor modulates macrophage phenotype and affects kidney ischemia-reperfusion injury during transplantation[J]. The Journal of Practical Medicine, 2025, 41(1): 23-29.

Figures/Tables 9

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References 21

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组别	肾小管损伤评分	Cr	BUN
Sham组	0.11 ± 0.33	32.33 ± 3.51	4.20 ± 0.16
RIRI组	2.56 ± 0.53^*	239.00 ± 123.45^*	37.79 ± 17.64^*
Inhibitor + RIRI组	1.56 ± 0.53^#&	197.57 ± 101.97^*&	17.65 ± 8.44^&
F值	21.62	4.191	8.64
P值	< 0.05	< 0.05	< 0.05

组别	KIM-1	RPA-1
Sham组	2.52 ± 1.83	11.16 ± 9.83
RIRI组	110.79 ± 13.59^*	141.15 ± 9.33^*
Inhibitor + RIRI组	47.46 ± 8.83^*&	54.05 ± 4.47^*&
F值	200.23	23.14
P值	< 0.01	< 0.01

组别	iNOS	IL-12	ARG-1
Sham组	1.76 ± 0.92	1.93 ± 1.48	10.45 ± 4.23
RIRI组	200.44 ± 14.95^*	23.89 ± 1.46^*	26.05 ± 5.37
Inhibitor + RIRI组	47.36 ± 2.08^*&	2.8 ± 0.75^&	122.23 ± 22.46^#&
F值	710.58	10.50	179.55
P值	< 0.05	< 0.05	< 0.05

组别	Dectin-1	Arg-1
Sham组	0.08 ± 0.04	0.19 ± 0.11
RIRI组	2.39 ± 1.96	2.85 ± 1.78
Inhibitor + RIRI组	18.40 ± 12.94^*&	12.27 ± 7.83^*&
F值	8.72	7.51
P值	< 0.05	< 0.05

组别	CD197	CD163
Sham组	21.04 ± 1.20	23.36 ± 1.15
RIRI组	32.67 ± 0.38^*	20.10 ± 3.62
Inhibitor + RIRI组	26.40 ± 1.49^*&	35.00 ± 1.46^*&
F值	7.20	33.43
P值	< 0.05	< 0.05

PKCβ inhibitor modulates macrophage phenotype and affects kidney ischemia-reperfusion injury during transplantation

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