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| Study on Acanthopanax senticosus Injection on alleviating renal injury in diabetic kidney disease mice by inhibiting TLR4/NF-κB signaling pathway |
| Hits 28 Download times 17 Received:September 02, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.01.18 |
| Key Words
diabetic kidney disease;Acanthopanth senticosus Injection;renal injury;TLR4/NF-κB signaling pathway;inflammation;apoptosis |
| Author Name | Affiliation | E-mail | | GUO Jinming | Handan Central Hospital, Handan 056001, China | | | FU Yongtao | Handan Central Hospital, Handan 056001, China | | | SUO Dawei | Handan Central Hospital, Handan 056001, China | | | JIANG Qilin | Handan Central Hospital, Handan 056001, China | | | BAI Min | Handan Central Hospital, Handan 056001, China | | | ZHENG Congcong | Handan Central Hospital, Handan 056001, China | | | WANG Liping | Handan Central Hospital, Handan 056001, China | ssm0518@126.com |
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| Abstract
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| [Objective] To investigate the effect of Acanthopanth senticosus Injection（ASI） regulating toll-like receptor 4/nuclear factor-κB（TLR4/NF-κB） signaling pathway on renal injury in diabetic kidney disease（DKD） mice. [Methods] The DKD mice model was established by high-fat diet combined with intrabitoneal injection of streptozotocin. And set up the normal control group，model group，ASI（75 mg/kg） group，ASI（75 mg/kg）+ressatovi（TAK-242，TLR4 inhibitor，0.5 mg/kg） group and ASI（75 mg/kg）+lipopolysaccharide（LPS，TLR4 agonist，10 mg/kg） group，with 10 mice in each group. After continuous administration for 8 weeks，the fasting blood glucose（FBG） and renal function indexes [24 h urinary protein（24 h UTP），uric acid（UA），blood urea nitrogen（BUN），serum creatinine（Scr）] of the mice were detected；the body mass and renal mass were weighed，and the renal index was calculated. The content of inflammatory factors [interleukin-1β（IL-1β），IL-6，tumor necrosis factor-α（TNF-α）] in renal tissue were detected by ELISA. The pathological changes of renal tissue were observed through HE staining. The renal fibrosis and renal cells apoptosis were detected through masson and TUNEL staining. The expression of TLR4，NF-κB p65 mRNA in renal tissue were detected by RT-PCR. The expression of TLR4，NF-κB p65，B-cell lymphoma-2（Bcl-2），Bcl-2 associated X protein（Bax），Caspase-3，Cleaved Caspase-3 proteins were detected by Western blot. [Results] Compared with the model group，the FBG，24 h UTP，UA，BUN，Scr，renal mass，renal index，IL-1β，IL-6，TNF-α were significantly decreased in ASI group and ASI+TAK-242 group，while the body mass was significantly increased（P<0.05）. The pathological changes and fibrosis of renal tissue，apoptosis of renal cells were significantly improved；and the renal tissue injury score，collagen volume fraction（CVF） and apoptosis index（AI） were significantly decreased（P<0.05）. The mRNA and protein expressions of TLR4，NF-κB p65 were significantly decreased，and the protein expression ratio of Bax/Bcl-2 and Cleaved Caspase-3/Caspase-3 were significantly decreased（P<0.05）. TAK-242 could significantly enhance the effects of ASI on FBG，renal function，body mass，renal coefficient，renal tissue lesion，fibrosis，apoptosis，TLR4/NF-κB signaling pathway related mRNA and protein expression in DKD mice. LPS significantly reversed the above effects of ASI on DKD mice. [Conclusion] ASI can alleviate renal injury and improve renal function in DKD mice，and its mechanism may be related to down-regulating TLR4/NF-κB signaling pathway，thereby inhibiting inflammation，renal fibrosis and apoptosis. |
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