Effects of berberine on Th17/Treg balance in autoimmune prostatitis rats by regulating AMPK/NF-κB signaling pathway

doi:10.11958/20221816

Abstract

Abstract:

Objective To investigate the influence of berberine on T helper cell 17 (Th17)/regulatory T cell (Treg) balance in autoimmune prostatitis (EAP) rats by regulating adenylate-activated protein kinase (AMPK)/nuclear factor-κB (NF-κB) signaling pathway. Methods Ninety SD male rats were randomly divided into the control group (normal feeding), the model group, the low-dose berberine group (25 mg/kg), the high-dose berberine group (50 mg/kg), the positive control group (40 mg/kg celecoxib) and the inhibitor group (50 mg/kg berberine + 0.2 mg/kg AMPK inhibitor compound C), with 15 rats in each group. Except for the control group, rats in other groups were all injected with complete Freund's adjuvant and prostate tissue mixed suspension in pelvic region and bilateral scapula to construct the EAP rat model. After successful modeling, drug treatment was carried out by gavage, once a day for four weeks. HE staining was used to observe the pathological conditions of prostate tissue in each group. Immunohistochemical method was used to detect the expressions of retinoic acid-related nuclear orphan receptor γt (RORγt) and forkhead box protein 3 (Foxp3) in rat prostate tissue. ELISA method was used to detect serum levels of interleukin (IL)-17 and IL-10 in rats. Flow cytometry was used to detect the ratio of Th17/Treg cells in peripheral blood of rats. Western blot assay was used to detect the expression of AMPK/NF-κB signaling pathway-related proteins in rat prostate tissue. Results Compared with the model group, there were pink secretions in prostate tissue cavity of rats in the low-dose and the high-dose berberine groups and the positive control group. The glandular epithelial cells were neatly arranged, and the inflammation subsided obviously. Serum IL-17 levels, peripheral blood Th17/Treg ratio, and RORγt and p-NF-κB p65/NF-κB p65 expression levels in prostate tissue were decreased, and serum IL-10 level, Foxp3, p-AMPK/AMPK and IκBα expression levels in prostate tissue were increased (P<0.05). After adding AMPK inhibitor compound C, the promoting effect of berberine on Th17/Treg balance in EAP rats was attenuated. Conclusion Berberine can promote Th17/Treg balance in EAP rats by regulating AMPK/NF-κB signaling pathway.

Key words: autoimmune prostatitis, berberine, AMPK/NF-κB, Th17/Treg balance

CLC Number:

R285.5

Figures/Tables 8

References 22

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组别	RORγt	Foxp3
对照组	0.11±0.02	0.51±0.05
模型组	0.45±0.05^a	0.13±0.02^a
小檗碱低剂量组	0.36±0.04^b	0.22±0.03^b
小檗碱高剂量组	0.22±0.03^bc	0.37±0.04^bc
阳性对照组	0.20±0.02^bc	0.38±0.04^bc
抑制剂组	0.39±0.04^d	0.17±0.02^d
F	69.635^＊＊	87.189^＊＊

组别	RORγt	Foxp3
对照组	0.11±0.02	0.51±0.05
模型组	0.45±0.05^a	0.13±0.02^a
小檗碱低剂量组	0.36±0.04^b	0.22±0.03^b
小檗碱高剂量组	0.22±0.03^bc	0.37±0.04^bc
阳性对照组	0.20±0.02^bc	0.38±0.04^bc
抑制剂组	0.39±0.04^d	0.17±0.02^d
F	69.635^＊＊	87.189^＊＊

组别	IL-17	IL-10
对照组	12.56±1.04	25.38±2.24
模型组	38.47±3.25^a	9.85±1.12^a
小檗碱低剂量组	26.38±3.17^b	14.63±1.35^b
小檗碱高剂量组	14.25±2.23^bc	22.52±2.17^bc
阳性对照组	13.19±1.12^bc	23.47±2.21^bc
抑制剂组	24.64±2.16^d	16.74±1.23^d
F	288.985^＊＊	169.376^＊＊

组别	IL-17	IL-10
对照组	12.56±1.04	25.38±2.24
模型组	38.47±3.25^a	9.85±1.12^a
小檗碱低剂量组	26.38±3.17^b	14.63±1.35^b
小檗碱高剂量组	14.25±2.23^bc	22.52±2.17^bc
阳性对照组	13.19±1.12^bc	23.47±2.21^bc
抑制剂组	24.64±2.16^d	16.74±1.23^d
F	288.985^＊＊	169.376^＊＊

组别	p-AMPK/ AMPK	p-NF-κB p65/ NF-κB p65	IκBα/ GAPDH
对照组	0.78±0.08	0.36±0.04	1.04±0.12
模型组	0.24±0.03^a	0.82±0.09^a	0.45±0.06^a
小檗碱低剂量组	0.46±0.05^b	0.67±0.08^b	0.62±0.08^b
小檗碱高剂量组	0.68±0.06^bc	0.43±0.04^bc	0.89±0.09^bc
阳性对照组	0.72±0.07^bc	0.41±0.05^bc	0.92±0.06^bc
抑制剂组	0.54±0.04^d	0.58±0.06^d	0.74±0.05^d
F	60.482^＊＊	38.417^＊＊	36.580^＊＊