Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/ NF-κB signaling pathway

doi:10.12122/j.issn.1673-4254.2024.09.17

Abstract

Abstract:

Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms. Methods Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ)-induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting. Results The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats. Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Key words: quercetin, diabetic nephropathy, HMGB1/ RAGE/ NF-κB signaling pathway

Yifan JIANG, Xiaorong LI, Jiayi GENG, Yongfeng CHEN, Bi TANG, Pinfang KANG. Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/ NF-κB signaling pathway[J]. Journal of Southern Medical University, 2024, 44(9): 1769-1775.

Figures/Tables 6

Tab.1 Comparisons of fasting blood glucose (FBG) and triglyceride (TG) among the groups (Mean±SD, n=6)

Group	FBG (mmol/L)	TG (mmol/L)
NC	5.88±0.51	0.96±0.16
HC	5.80±0.33	1.48±0.19**
DM	26.67±5.65**	3.82±0.35**
DMQ	19.28±1.45^##	2.95±0.29^##

Tab.2 Comparison of blood urea nitrogen (BUN), serum creatinine (Scr), 24-hour urinary protein level (24 h-UP) and renal hypertrophy index (RHI) among the groups (Mean±SD, n=6 )

Group	BUN (mmol/L)	Scr (μmol/L)	24 h-UP (mg/24 h)	RHI (×10^-³)
NC	8.11±0.45	35.9±2.4	16.03±2.04	5.3±0.3
HC	15.4±0.68**	45.9±3.3**	36.25±3.20**	6.7±0.5
DM	18.45±0.30**	59.1±3.1**	65.42±3.59**	14.6±0.6**
DMQ	12.51±0.25^##	44.9±3.1^##	42.74±5.96^##	9.6±0.8^##

Fig.1 Comparisons of serum levels of IL-1β (A), IL-6 (B) and TNF-α (C) among the groups (Mean±SD, n=6). **P<0.01 vs NC group, ##P<0.01 vs DM group.

Fig.2 HE staining of rat kidney tissues in each group. A: NC group; B: HC group; C: DM group; D: DMQ group.

Fig.3 Immunohistochemical results of NF-κB and relative protein expressions of HMGB1, RAGE and NF-κB in rat kidney tissues in each group (Mean±SD, n=4). A, B: Immunohistochemical results for NF-κB and quantitative analysis of its expression levels (a: NC group; b: HC group; c: DM group; d: DMQ group). C: Western blotting results of HMGB1, RAGE, NF-κB and GAPDH. D-F: HMGB1, RAGE and NF-κB protein levels normalized by GAPDH levels. **P<0.01 vs NC group; ##P<0.01 vs DM group.

Fig.4 Comparisons of relative protein expressions of Bax, Bcl-2 and caspase-3 in rat kidney tissues among the groups (Mean±SD, n=4). A: Western blotting results of Bax, Bcl-2, caspase-3 and GAPDH. B, C: Bax/Bcl-2 and caspase-3 protein levels normalized by GAPDH levels. **P<0.01 vs NC group; ##P<0.01 vs DM group.

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