Protective effect of salidroside on septic acute kidney injury in rats by inhibiting phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signal pathway

doi:10.3877/cma.j.issn.1674-6880.2024.03.003

Abstract

Abstract:

Objective

To explore the protective effect of salidroside (SLDS) on septic acute kidney injury (SAKI) in rats by regulating the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.

Methods

Forty Sprague-Dawley rats were randomly divided into four groups, namely the control group, the sham group, the cecal ligation and perforation group (CLP group) and the SLDS pretreatment group (CLP + SLDS group), 10 rats in each group. We assessed the pathological damage of kidney tissue in each group, and used enzyme-linked immunosorbent assay (ELISA) to detect the levels of serum creatinine (Scr), plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule 1 (pKIM-1) in rats. Meanwhile, we detected the expression levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in plasma. We used the TUNEL method to observe renal cell apoptosis, real-time fluorescence quantitative PCR (RT-qPCR) method to detect cysteinyl aspartate specific proteinase-3 (Caspase-3), B-cell lymphoma-2 associated X (Bax) and B-cell lymphomato-2 (Bcl-2) messenger RNA (mRNA) expression, and western-blotting method to detect phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) protein expression.

Results

There were significant differences in the pathological damage score, Scr, pKIM-1, pNGAL, TNF-α, IL-1β, IL-4, IL-4, IL-10, number of apoptosis, Caspase-3 mRNA, Bax mRNA, Bcl-2 mRNA, p-PI3K protein, p-AKT protein and p-mTOR protein in kidney tissue among the four groups (F = 132.603, 626.719, 216.573, 335.719, 368.219, 403.612, 169.901, 181.281, 169.312, 960.912, 1 479.000, 32.221, 178.346, 137.560, 136.241; all P < 0.001). Compared with the sham group, the pathological damage of kidney tissue was worsened, the levels of Scr, pKIM-1, pNGAL, TNF-α, IL-1β, Caspase-3 mRNA, Bax mRNA, p-PI3K protein, p-AKT protein and p-mTOR protein in kidney tissue and the number of renal cell apoptosis were significantly increased, and the levels of IL-4, IL-10 and Bcl-2 mRNA were decreased in the CLP group (all P < 0.05). Compared with the CLP group, the pathological damage of kidney tissue was reduced, the levels of Scr, pKIM-1, pNGAL, TNF-α, IL-1β, Caspase-3 mRNA, Bax mRNA, p-PI3K protein, p-AKT protein and p-mTOR protein in kidney tissue and the number of renal cell apoptosis were significant decreased, and the levels of IL-4, IL-10 and Bcl-2 mRNA were increased in the CLP + SLDS group (all P < 0.05).

Conclusion

SLDS has a significant protective effect on SAKI by inhibiting the PI3K/AKT/mTOR signaling pathway.

Key words: Salidroside, Sepsis, Acute kidney injury, Phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin, Signaling pathway

Heng Fan, Min Sun, Jianhua Zhu. Protective effect of salidroside on septic acute kidney injury in rats by inhibiting phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signal pathway[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(03): 188-195.

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Figures/Tables 7

References 20

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组别	只数	肾组织病理损伤评分（分）	Scr（μmol/L）	pKIM-1（μg/L）	pNGAL（μg/L）
Control组	10	0.20 ± 0.16	21.2 ± 1.1	12.2 ± 0.4	13.0 ± 0.4
Sham组	10	0.40 ± 0.16	19.8 ± 1.1	12.0 ± 0.4	12.5 ± 0.4
CLP组	10	3.80 ± 0.13^a	183.3 ± 3.7^a	37.7 ± 1.4^a	77.2 ± 2.6^a
CLP + SLDS组	10	2.40 ± 0.16^b	107.3 ± 4.9^b	24.3 ± 0.6^b	32.6 ± 1.0^b
F值		132.603	626.719	216.573	335.719
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	只数	肾组织病理损伤评分（分）	Scr（μmol/L）	pKIM-1（μg/L）	pNGAL（μg/L）
Control组	10	0.20 ± 0.16	21.2 ± 1.1	12.2 ± 0.4	13.0 ± 0.4
Sham组	10	0.40 ± 0.16	19.8 ± 1.1	12.0 ± 0.4	12.5 ± 0.4
CLP组	10	3.80 ± 0.13^a	183.3 ± 3.7^a	37.7 ± 1.4^a	77.2 ± 2.6^a
CLP + SLDS组	10	2.40 ± 0.16^b	107.3 ± 4.9^b	24.3 ± 0.6^b	32.6 ± 1.0^b
F值		132.603	626.719	216.573	335.719
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	只数	TNF-α	IL-1β	IL-4	IL-10
Control组	10	12.5 ± 0.4	11.7 ± 0.4	48.2 ± 0.8	42.2 ± 0.7
Sham组	10	12.7 ± 0.4	14.6 ± 0.5	48.5 ± 0.8	42.8 ± 0.6
CLP组	10	36.0 ± 0.8^a	41.5 ± 0.8^a	26.3 ± 0.8^a	22.3 ± 0.8^a
CLP + SLDS组	10	24.3 ± 0.6^b	28.1 ± 1.0^b	40.4 ± 0.7^b	33.7 ± 0.6^b
F值		368.219	403.612	169.901	181.281
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	只数	TNF-α	IL-1β	IL-4	IL-10
Control组	10	12.5 ± 0.4	11.7 ± 0.4	48.2 ± 0.8	42.2 ± 0.7
Sham组	10	12.7 ± 0.4	14.6 ± 0.5	48.5 ± 0.8	42.8 ± 0.6
CLP组	10	36.0 ± 0.8^a	41.5 ± 0.8^a	26.3 ± 0.8^a	22.3 ± 0.8^a
CLP + SLDS组	10	24.3 ± 0.6^b	28.1 ± 1.0^b	40.4 ± 0.7^b	33.7 ± 0.6^b
F值		368.219	403.612	169.901	181.281
P值		< 0.001	< 0.001	< 0.001	< 0.001

组别	只数	细胞凋亡数量（个）	Caspase-3 mRNA	Bax mRNA	Bcl-2 mRNA
Control组	10	5.7 ± 1.1	0.100 ± 0.007	0.100 ± 0.004	0.424 ± 0.017
Sham组	10	5.9 ± 1.2	0.132 ± 0.007	0.124 ± 0.004	0.438 ± 0.019
CLP组	10	37.0 ± 6.2^a	0.576 ± 0.010^a	0.531 ± 0.008^a	0.261 ± 0.013^a
CLP + SLDS组	10	12.8 ± 3.9^b	0.414 ± 0.009^b	0.378 ± 0.007^b	0.342 ± 0.008^b
F值		169.312	960.912	1 479.000	32.221
P值		< 0.001	< 0.001	< 0.001	< 0.001

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